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Reis E Silva R, Portal TM, Nogueira NDS, Nogueira TDS, Mello ADA, Monteiro-de-Barros C. Paraquat neurotoxicity: Oxidative stress and neuronal dysfunction in the ascidian brain. Comp Biochem Physiol C Toxicol Pharmacol 2025; 290:110128. [PMID: 39855440 DOI: 10.1016/j.cbpc.2025.110128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 12/05/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
Paraquat (PQ) is a widely used herbicide; however, it has been linked to various diseases, including an increased risk of developing Parkinsonism. To study this, invertebrates such as ascidians have been used. They have a simple nervous system and are considered an emerging model for the study of neurodegenerative diseases. Here, we investigated the effects of PQ in the brain of the ascidian Styela plicata. We performed behavioral tests, assessed morphology, and monitored oxidative stress and the expression of tyrosine hydroxylase (TH) and caspase-3 (Casp 3) using immunofluorescence. In the presence of PQ, siphon movement was reduced and cortical thickness was increased. In addition, an observed increase in ROS was detected, along with attenuated SOD and CAT activities and increased LPO production. Interestingly, PQ downregulated the expression of TH and upregulated that of Casp 3. We conclude that PQ-induced oxidative stress leads to the death of catecholaminergic neurons in the S. plicata brain.
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Affiliation(s)
- Rebeca Reis E Silva
- Laboratório Integrado de Biociências Translacionais - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação em Produtos Bioativos e Biociências - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil
| | - Taynan Motta Portal
- Laboratório Integrado de Biociências Translacionais - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação em Produtos Bioativos e Biociências - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação em Biociências e Biotecnologia - Universidade Estadual do Norte Fluminense Darcy Ribeiro - UENF - Campos dos Goytacazes, Rio de Janeiro, RJ, Brazil
| | - Nathany da Silva Nogueira
- Laboratório Integrado de Biociências Translacionais - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação Multicêntrico em Ciências Fisiológicas - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil
| | - Thuany da Silva Nogueira
- Laboratório Integrado de Biociências Translacionais - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação Multicêntrico em Ciências Fisiológicas - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil
| | - Andressa de Abreu Mello
- Pós-Graduação em Ciências Biológicas - Instituto de Biofísica Carlos Chagas Filho - Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil
| | - Cintia Monteiro-de-Barros
- Laboratório Integrado de Biociências Translacionais - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação em Produtos Bioativos e Biociências - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação Multicêntrico em Ciências Fisiológicas - Instituto de Biodiversidade e Sustentabilidade - NUPEM - Universidade Federal do Rio de Janeiro - UFRJ, Macaé, RJ, Brazil; Pós-Graduação em Biociências e Biotecnologia - Universidade Estadual do Norte Fluminense Darcy Ribeiro - UENF - Campos dos Goytacazes, Rio de Janeiro, RJ, Brazil.
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Tieu K, Salehe SS, Brown HJ. Toxin-Induced Animal Models of Parkinson's Disease. Cold Spring Harb Perspect Med 2025; 15:a041643. [PMID: 38951030 PMCID: PMC11875089 DOI: 10.1101/cshperspect.a041643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/03/2024]
Abstract
The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms and evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. Herein, we systematically review the literature over the past decade. Some models no longer serve the purpose of PD models. The primary objectives of this review are: First, to assist new investigators in navigating through available animal models and making appropriate selections based on the objective of the study. Emphasis will be placed on common toxin-induced murine models. And second, to provide an overview of basic technical requirements for assessing the nigrostriatal pathway's pathology, structure, and function.
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Affiliation(s)
- Kim Tieu
- Department of Environmental Health Sciences, Florida International University, Miami, Florida 33199, USA
- Biomolecular Sciences Institute, Florida International University, Miami, Florida 33199, USA
| | - Said S Salehe
- Department of Environmental Health Sciences, Florida International University, Miami, Florida 33199, USA
| | - Harry J Brown
- Department of Environmental Health Sciences, Florida International University, Miami, Florida 33199, USA
- Biomolecular Sciences Institute, Florida International University, Miami, Florida 33199, USA
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Atterling Brolin K, Schaeffer E, Kuri A, Rumrich IK, Schumacher Schuh AF, Darweesh SK, Kaasinen V, Tolppanen A, Chahine LM, Noyce AJ. Environmental Risk Factors for Parkinson's Disease: A Critical Review and Policy Implications. Mov Disord 2025; 40:204-221. [PMID: 39601461 PMCID: PMC11832802 DOI: 10.1002/mds.30067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/13/2024] [Accepted: 11/04/2024] [Indexed: 11/29/2024] Open
Abstract
The age-standardized prevalence of Parkinson's disease (PD) has increased substantially over the years and is expected to increase further. This emphasizes the need to identify modifiable risk factors of PD, which could form a logical entry point for the prevention of PD. The World Health Organization (WHO) has recommended reducing exposure to specific environmental factors that have been reported to be associated with PD, in particular pesticides, trichloroethylene (TCE), and air pollution. In this review we critically evaluate the epidemiological and biological evidence on the associations of these factors with PD and review evidence on whether these putative associations are causal. We conclude that when considered in isolation, it is difficult to determine whether these associations are causal, in large part because of the decades-long lag between relevant exposures and the incidence of manifest PD. However, when considered in tandem with evidence from complementary research lines (such as animal models), it is increasingly likely that these associations reflect harmful causal effects. Fundamentally, whilst we highlight some evidence gaps that require further attention, we believe the current evidence base is sufficiently strong enough to support our call for stronger policy action. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Kajsa Atterling Brolin
- Translational Neurogenetics Unit, Department of Experimental Medical ScienceLund UniversityLundSweden
- Centre for Preventive Neurology, Wolfson Institute of Population HealthQueen Mary University of LondonLondonUK
| | - Eva Schaeffer
- Department of Neurology, University Hospital Schleswig‐HolsteinCampus Kiel and Kiel UniversityKielGermany
| | - Ashvin Kuri
- Centre for Preventive Neurology, Wolfson Institute of Population HealthQueen Mary University of LondonLondonUK
| | - Isabell Katharina Rumrich
- School of PharmacyUniversity of Eastern FinlandFinland
- Department of Health ProtectionFinnish Institute for Health and WelfareFinland
| | - Artur Francisco Schumacher Schuh
- Departamento de FarmacologiaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
- Serviço de NeurologiaHospital de Clínicas de Porto AlegrePorto AlegreBrazil
| | - Sirwan K.L. Darweesh
- Radboud University Medical CenterDonders Institute for Brain, Cognition and Behaviour, Department of Neurology, Center of Expertise for Parkinson & Movement DisordersNijmegenThe Netherlands
| | - Valtteri Kaasinen
- Clinical NeurosciencesUniversity of TurkuTurkuFinland
- NeurocenterTurku University HospitalTurkuFinland
| | | | - Lana M. Chahine
- Department of NeurologyUniversity of PittsburghPittsburghPennsylvaniaUSA
| | - Alastair J. Noyce
- Centre for Preventive Neurology, Wolfson Institute of Population HealthQueen Mary University of LondonLondonUK
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Xu Y, Su Y, Cai S, Yao Y, Chen X. Environmental and occupational exposure to organochlorine pesticides associated with Parkinson's disease risk: A systematic review and meta-analysis based on epidemiological evidence. Public Health 2024; 237:374-386. [PMID: 39520734 DOI: 10.1016/j.puhe.2024.10.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 10/22/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
OBJECTIVES The purpose of this study was to analyze the association between environmental and occupational organochlorine pesticides (OCPs) exposure and Parkinson's disease (PD) risk. STUDY DESIGN Systematic review and meta-analysis. METHODS A comprehensive search of articles before March 18, 2024, was conducted through PubMed, Cochrane, Embase, Medlin and Web of Science databases, and the relevant data were expressed as odds ratios (OR) and 95 % confidence intervals (CI). Newcastle-Ottawa Scale (NOS) was used to evaluate literature quality. STATA (Version 11.0) was used for analysis. RESULTS This meta-analysis included 17 case-control studies. The results showed that OCPs exposure increased PD risk, including seven blood sample assessment exposure (BOCPs) studies (OR = 1.54, 95 % CI = 1.32-1.79) and 10 indirect assessment exposure (IOCPs) studies (OR = 1.19, 95 % CI = 1.04-1.35). Location subgroup analysis showed that OCPs was positively associated with PD risk in Asia, while there was no statistical significance in North America and Europe. The IOCPs functional subclasses subgroup results suggested that organochlorine insecticides were significantly associated with PD risk (OR = 1.18, 95%CI = 1.03-1.37). Study time may be a factor of high heterogeneity in BOCPs. In addition, BOCPs (OR = 1.49, 95%CI = 1.28-1.74) and IOCPs (OR = 1.10, 95%CI = 0.95-1.26) showed different results with PD risk. CONCLUSIONS Study suggests that OCPs exposure may be a risk factor for PD, but there may be location and OCPs type differences.
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Affiliation(s)
- Yang Xu
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, China
| | - Yan Su
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, China
| | - Sheng Cai
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, China
| | - Yuanhang Yao
- Materials Science and Engineering, School of Physics and Materials Engineering, Hefei Normal University, Hefei, Anhui, 238076, China
| | - Xianwen Chen
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230000, China.
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5
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Oliveira GR, Gallas-Lopes M, Chitolina R, Bastos LM, Portela SM, Stahlhofer-Buss T, Gusso D, Gomez R, Wyse ATS, Herrmann AP, Piato A. Evaluation of behavioral and neurochemical changes induced by carbofuran in zebrafish (Danio rerio). Comp Biochem Physiol C Toxicol Pharmacol 2024; 283:109969. [PMID: 38925284 DOI: 10.1016/j.cbpc.2024.109969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 06/17/2024] [Accepted: 06/22/2024] [Indexed: 06/28/2024]
Abstract
Carbofuran (CF) is a carbamate class pesticide, widely used in agriculture for pest control in crops. This pesticide has high toxicity in non-target organisms, and its presence in the environment poses a threat to the ecosystem. Research has revealed that this pesticide acts as an inhibitor of acetylcholinesterase (AChE), inducing an accumulation of acetylcholine in the brain. Nonetheless, our understanding of CF impact on the central nervous system remains elusive. Therefore, this study explored how CF influences behavioral and neurochemical outcomes in adult zebrafish. The animals underwent a 96-hour exposure protocol to different concentrations of CF (5, 50, and 500 μg/L) and were subjected to the novel tank (NTT) and social preference tests (SPT). Subsequently, they were euthanized, and their brains were extracted to evaluate neurochemical markers associated with oxidative stress and AChE levels. In the NTT and SPT, CF did not alter the evaluated behavioral parameters. Furthermore, CF did not affect the levels of AChE, non-protein sulfhydryl groups, and thiobarbituric acid reactive species in the zebrafish brain. Nevertheless, further investigation is required to explore the effects of environmental exposure to this compound on non-target organisms.
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Affiliation(s)
- Giovana R Oliveira
- Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Matheus Gallas-Lopes
- Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Rafael Chitolina
- Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Leonardo M Bastos
- Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Stefani M Portela
- Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Thailana Stahlhofer-Buss
- Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Darlan Gusso
- Programa de Pós-graduação em Ciências Biológicas, Bioquímica, Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Rosane Gomez
- Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Angela T S Wyse
- Programa de Pós-graduação em Ciências Biológicas, Bioquímica, Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Ana P Herrmann
- Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
| | - Angelo Piato
- Programa de Pós-graduação em Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Laboratório de Psicofarmacologia e Comportamento (LAPCOM), Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
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6
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Kumar D, Sinha SN. Chronic exposures to cholinesterase-inhibiting pesticides adversely affects the health of agricultural workers in India. ENVIRONMENTAL RESEARCH 2024; 252:118961. [PMID: 38642639 DOI: 10.1016/j.envres.2024.118961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 04/12/2024] [Accepted: 04/15/2024] [Indexed: 04/22/2024]
Abstract
Biomonitoring of pesticide exposure has become a public concern because of its potential health effects. The present study investigated the acetylcholinesterase (AChE) inhibitory levels and their associated health effects in agricultural areas in Telangana, India. This cross-sectional included 341 exposed participants and 152 control participants from agricultural areas. A structured questionnaire was completed and blood and urine samples were collected to measure pesticides, dialkyle phosphate (DAP) metabolites, and AChE activity using liquid chromatography-tandem mass spectrometry and reversed-phase high-performance liquid chromatography. twenty-eight pesticides were detected in blood samples at concentrations ranging 0.42-45.77 ng/mL. Six DAP metabolites were also measured in urine, and all DAP metabolites were significantly higher in the exposed group. AChE activity is significantly reduced in individuals exposed for >10 years, raising concerns regarding possible neurological disorders. These results emphasise the urgent need to investigate the health effects of pesticides exposure, especially in agriculture.
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Affiliation(s)
- Dileshwar Kumar
- Division of Food Safety, Indian Council of Medical Research - National Institute of Nutrition, Jamai-Osmania, Hyderabad, 500007, India; Department of Biochemistry Osmania University, Hyderabad, 500007, India.
| | - Sukesh Narayan Sinha
- Division of Food Safety, Indian Council of Medical Research - National Institute of Nutrition, Jamai-Osmania, Hyderabad, 500007, India.
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7
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Schaffner SL, Casazza W, Artaud F, Konwar C, Merrill SM, Domenighetti C, Schulze-Hentrich JM, Lesage S, Brice A, Corvol JC, Mostafavi S, Dennis JK, Elbaz A, Kobor MS. Genetic variation and pesticide exposure influence blood DNA methylation signatures in females with early-stage Parkinson's disease. NPJ Parkinsons Dis 2024; 10:98. [PMID: 38714693 PMCID: PMC11076573 DOI: 10.1038/s41531-024-00704-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 04/05/2024] [Indexed: 05/10/2024] Open
Abstract
Although sex, genetics, and exposures can individually influence risk for sporadic Parkinson's disease (PD), the joint contributions of these factors to the epigenetic etiology of PD have not been comprehensively assessed. Here, we profiled sex-stratified genome-wide blood DNAm patterns, SNP genotype, and pesticide exposure in agricultural workers (71 early-stage PD cases, 147 controls) and explored replication in three independent samples of varying demographics (n = 218, 222, and 872). Using a region-based approach, we found more associations of blood DNAm with PD in females (69 regions) than in males (2 regions, Δβadj| ≥0.03, padj ≤ 0.05). For 48 regions in females, models including genotype or genotype and pesticide exposure substantially improved in explaining interindividual variation in DNAm (padj ≤ 0.05), and accounting for these variables decreased the estimated effect of PD on DNAm. The results suggested that genotype, and to a lesser degree, genotype-exposure interactions contributed to variation in PD-associated DNAm. Our findings should be further explored in larger study populations and in experimental systems, preferably with precise measures of exposure.
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Affiliation(s)
- S L Schaffner
- Edwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
| | - W Casazza
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada
- Bioinformatics Graduate Program, University of British Columbia, Vancouver, BC, Canada
| | - F Artaud
- Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, 94805, Villejuif, France
| | - C Konwar
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada
| | - S M Merrill
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada
| | - C Domenighetti
- Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, 94805, Villejuif, France
| | - J M Schulze-Hentrich
- Department of Genetics/Epigenetics, Faculty NT, Saarland University, 66041, Saarbrücken, Germany
| | - S Lesage
- Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France
| | - A Brice
- Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France
| | - J C Corvol
- Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France
- Sorbonne University, Assistance Publique Hôpitaux de Paris, Paris Brain Insitute - ICM, Inserm, CNRS, Department of Neurology and CIC Neurosciences, Pitié-Salpêtrière Hospital, Paris, France
| | - S Mostafavi
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Bioinformatics Graduate Program, University of British Columbia, Vancouver, BC, Canada
- Paul Allen School of Computer Science and Engineering, University of Washington, Seattle, WA, USA
| | - J K Dennis
- Edwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
- Bioinformatics Graduate Program, University of British Columbia, Vancouver, BC, Canada
| | - A Elbaz
- Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, 94805, Villejuif, France
| | - M S Kobor
- Edwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
- Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada.
- Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
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8
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Silva RH, Lopes-Silva LB, Cunha DG, Becegato M, Ribeiro AM, Santos JR. Animal Approaches to Studying Risk Factors for Parkinson's Disease: A Narrative Review. Brain Sci 2024; 14:156. [PMID: 38391730 PMCID: PMC10887213 DOI: 10.3390/brainsci14020156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/25/2024] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson's disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease's etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment.
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Affiliation(s)
- R H Silva
- Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo 04021-001, SP, Brazil
| | - L B Lopes-Silva
- Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo 04021-001, SP, Brazil
| | - D G Cunha
- Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo 04021-001, SP, Brazil
| | - M Becegato
- Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo 04021-001, SP, Brazil
| | - A M Ribeiro
- Laboratory of Neuroscience and Bioprospecting of Natural Products, Department of Biosciences, Universidade Federal de São Paulo, Santos 11015-020, SP, Brazil
| | - J R Santos
- Behavioral and Evolutionary Neurobiology Laboratory, Department of Biosciences, Federal University of Sergipe, Itabaiana 49500-000, SE, Brazil
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9
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Sharma P, Mittal P. Paraquat (herbicide) as a cause of Parkinson's Disease. Parkinsonism Relat Disord 2024; 119:105932. [PMID: 38008593 DOI: 10.1016/j.parkreldis.2023.105932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 11/04/2023] [Accepted: 11/13/2023] [Indexed: 11/28/2023]
Abstract
The four features of Parkinson's disease (PD), which also manifests other non-motor symptoms, are bradykinesia, tremor, postural instability, and stiffness. The pathogenic causes of Parkinsonism include Lewy bodies, intracellular protein clumps of αsynuclein, and the degeneration of dopaminergic neurons in the substantia nigra's pars compacta region. The pathophysiology of PD is still poorly understood due to the complexity of the illness. The apoptotic cell death of neurons in PD, however, has been linked to a variety of intracellular mechanisms, according to a wide spectrum of study. The endoplasmic reticulum's stress, decreased levels of neurotrophic factors, oxidative stress, mitochondrial dysfunction, catabolic alterations in dopamine, and decreased activity of tyrosine hydroxylase are some of these causes. The herbicide paraquat has been used in laboratory studies to create a variety of PD pathological features in numerous in-vitro and in-vivo animals. Due to the unique neurotoxicity that paraquat causes, understanding of the pathophysiology of PD has changed. Parkinson's disease (PD) is more likely to develop among people exposed to paraquat over an extended period of time, according to epidemiological studies. Thanks to this paradigm, the hunt for new therapy targets for PD has expanded. In both in-vitro and in-vivo models, the purpose of this study is to summarise the relationship between paraquat exposure and the onset of Parkinson's disease (PD).
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Affiliation(s)
| | - Payal Mittal
- University Institute of Pharma Sciences, Mohali, Punjab, India.
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10
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Walsh L, Hill C, Ross RP. Impact of glyphosate (Roundup TM) on the composition and functionality of the gut microbiome. Gut Microbes 2023; 15:2263935. [PMID: 38099711 PMCID: PMC10561581 DOI: 10.1080/19490976.2023.2263935] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 09/24/2023] [Indexed: 12/18/2023] Open
Abstract
Glyphosate, the active ingredient in the broad-spectrum herbicide RoundupTM, has been a topic of discussion for decades due to contradictory reports of the effect of glyphosate on human health. Glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) of the shikimic pathway producing aromatic amino acids in plants, a mechanism that suggests that the herbicide would not affect humans as this pathway is not found in mammals. However, numerous studies have implicated glyphosate exposure in the manifestation of a variety of disorders in the human body. This review specifically outlines the potential effect of glyphosate exposure on the composition and functionality of the gut microbiome. Evidence has been building behind the hypothesis that the composition of each individual gut microbiota significantly impacts health. For this reason, the potential of glyphosate to inhibit the growth of beneficial microbes in the gut or alter their functionality is an important topic that warrants further consideration.
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Affiliation(s)
- Lauren Walsh
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Colin Hill
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - R. Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
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11
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Otaiku AI. Religiosity and Risk of Parkinson's Disease in England and the USA. JOURNAL OF RELIGION AND HEALTH 2023; 62:4192-4208. [PMID: 35763200 PMCID: PMC10682218 DOI: 10.1007/s10943-022-01603-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/15/2022] [Indexed: 05/11/2023]
Abstract
Parkinson's disease (PD) is associated with low religiosity cross-sectionally. Whether low religiosity might be associated with an increased risk for developing PD is unknown. This study investigated whether low religiosity in adulthood is associated with increased risk for developing PD. A population-based prospective cohort study was conducted. Participants from the English Longitudinal Study of Aging and the Midlife in the United States study who were free from PD at baseline (2004-2011) and completed questionnaires on self-reported religiosity, were included in a pooled analysis. Incident PD was based on self-report. Multivariable logistic regression was used to estimate odds ratios (OR) for developing PD according to baseline religiosity, with adjustment for sociodemographic characteristics, health and lifestyle factors and engagement in religious practices. Among 9,796 participants in the pooled dataset, 74 (0.8%) cases of incident PD were identified during a median follow-up of 8.1 years. In the fully adjusted model, compared with participants who considered religion very important in their lives at baseline, it was found that participants who considered religion "not at all important" in their lives had a tenfold risk of developing PD during follow-up (OR, 9.99; 95% CI 3.28-30.36). Moreover, there was a dose-response relationship between decreasing religiosity and increasing PD risk (P < 0.001 for trend). These associations were similar when adjusting for religious upbringing and when cases occurring within the first two years of follow-up were excluded from the analysis. The association was somewhat attenuated when religious practices were removed from the model as covariates, though it remained statistically significant (OR for "not at all important" vs. "very important", 2.26; 95% CI 1.03-4.95) (P < 0.029 for trend). This longitudinal study provides evidence for the first time that low religiosity in adulthood may be a strong risk factor for developing PD.
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Affiliation(s)
- Abidemi I Otaiku
- Department of Neurology, Birmingham City Hospital, Dudley Road, Birmingham, B18 7QH, UK.
- Centre for Human Brain Health, University of Birmingham, Birmingham, UK.
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12
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Hsiao CC, Yang AM, Wang C, Lin CY. Association between glyphosate exposure and cognitive function, depression, and neurological diseases in a representative sample of US adults: NHANES 2013-2014 analysis. ENVIRONMENTAL RESEARCH 2023; 237:116860. [PMID: 37562738 DOI: 10.1016/j.envres.2023.116860] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 07/13/2023] [Accepted: 08/07/2023] [Indexed: 08/12/2023]
Abstract
Glyphosate, the most widely used herbicide globally, has been linked to neurological impairments in some occupational studies. However, the potential neurotoxic effects of glyphosate exposure in the general population are still not fully understood. We conducted analyses on existing data collected from 1532 adults of the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to explore the possible relationship between glyphosate exposure and cognitive function, depressive symptoms, disability, and neurological medical conditions. Our results showed a significant negative association between urinary glyphosate levels and the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD-WLT) trial 3 recall and delayed recall scores in both models, with ß coefficients of -0.288 (S.E. = 0.111, P = 0.021) and -0.426 (S.E. = 0.148, P = 0.011), respectively. Furthermore, the odds ratio did not show a significant increase with the severity of depressive symptoms with a one-unit increase in ln-glyphosate levels. However, the odds ratio for severe depressive symptoms was significantly higher than for no symptoms (odds ratio = 4.148 (95% CI = 1.009-17.133), P = 0.049). Notably, the odds ratio showed a significant increase for individuals with serious hearing difficulty (odds ratio = 1.354 (95% CI = 1.018-1.800), P = 0.039) with a one-unit increase in ln-glyphosate levels, but not for other neurological medical conditions. In conclusion, our findings provide the first evidence that glyphosate exposure may be associated with neurological health outcomes in the US adult population. Additional investigation is necessary to understand the potential mechanisms and clinical significance of these correlations.
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Affiliation(s)
- Ching Chung Hsiao
- Department of Nephrology, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - An-Ming Yang
- Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, 237, Taiwan; Department of Healthcare Management, Yuanpei University of Medical Technology, Hsinchu, 300, Taiwan.
| | - ChiKang Wang
- Department of Environmental Engineering and Health, Yuanpei University of Medical Technology, Hsinchu, 300, Taiwan.
| | - Chien-Yu Lin
- Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, 237, Taiwan; Department of Environmental Engineering and Health, Yuanpei University of Medical Technology, Hsinchu, 300, Taiwan; School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, 242, Taiwan.
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13
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Aamodt WW, Willis AW, Dahodwala N. Racial and Ethnic Disparities in Parkinson Disease: A Call to Action. Neurol Clin Pract 2023; 13:e200138. [PMID: 37064587 PMCID: PMC10101714 DOI: 10.1212/cpj.0000000000200138] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 12/01/2022] [Indexed: 03/18/2023]
Abstract
Health disparities are pervasive in the United States. In the field of Parkinson disease (PD), profound racial and ethnic disparities exist in diagnosis, treatment, and research participation, leading to differential health outcomes and lack of generalizable research data. Racial and ethnic disparities not only limit our understanding of this complex heterogeneous disorder but also hamper our ability to provide new evidence-based care for America's most vulnerable populations. In this report, we summarize findings from our comprehensive white paper for the Michael J. Fox Foundation that reviews the current state of knowledge on racial and ethnic disparities in PD care in the following areas: epidemiology, etiology, phenotype and diagnosis, treatment, and research. We also identify knowledge gaps and necessary policy changes to ensure equitable, high-value care for all persons with PD. These strategies are designed to help identify and reduce health disparities among persons with PD and may serve as a model for other neurologic diseases.
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Affiliation(s)
- Whitley W Aamodt
- Department of Neurology (WWA, AWW, ND); and Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research (WWA, AWW), University of Pennsylvania, Philadelphia, PA
| | - Allison W Willis
- Department of Neurology (WWA, AWW, ND); and Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research (WWA, AWW), University of Pennsylvania, Philadelphia, PA
| | - Nabila Dahodwala
- Department of Neurology (WWA, AWW, ND); and Translational Center of Excellence for Neuroepidemiology and Neurology Outcomes Research (WWA, AWW), University of Pennsylvania, Philadelphia, PA
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14
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Chambers-Richards T, Su Y, Chireh B, D'Arcy C. Exposure to toxic occupations and their association with Parkinson's disease: a systematic review with meta-analysis. REVIEWS ON ENVIRONMENTAL HEALTH 2023; 38:65-83. [PMID: 34796708 DOI: 10.1515/reveh-2021-0111] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 11/03/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVES Earlier longitudinal reviews on environmental and occupational toxins and Parkinson's disease (PD) risk have limitations. This study aimed to determine the strength of association between three types of toxic occupational exposures and the occurrence of PD by diagnostic methods. METHODS A search was conducted of EMBASE, PubMed/Medline, Toxnet, LILACS, and Cochrane Library databases for longitudinal studies that assessed toxic occupational exposure, Parkinsonian, or related disorders, diagnosed by International Classification of Diseases (ICD) codes, medical records, or confirmation by a neurologist/nurse, and published in the English language from January 1990 to July 2021. Pooled risk ratios (RR) estimates were produced using random-effects models. Systematic review with meta-analysis synthesized the results. Study quality, heterogeneity, and publication bias were examined. High-quality articles that met the inclusion criteria were analyzed. RESULTS Twenty-four articles were used in the analyses. The pooled RR for electromagnetic exposure and PD were (RR=1.03, 95% confidence interval [CI] 0.91-1.16) while the pooled RR between PD and metal and pesticide exposure were (RR=1.07, 95% CI 0.92-1.24) and (RR=1.41, 95% CI 1.20-1.65), respectively. Pooled RR for methods of diagnosis and their associations with PD were: confirmation by a neurologist or nurse (RR=2.17, 95% CI 1.32-3.54); ICD codes (RR=1.14, 95% CI 1.03-1.26), and medical records (RR=1.06, 95% CI 0.92-1.21). CONCLUSIONS Our systematic review provides robust evidence that toxic occupational exposures are significant risk factors for PD especially those diagnosed by neurologists or nurses using standardized methods.
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Affiliation(s)
| | - Yingying Su
- School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada
| | | | - Carl D'Arcy
- School of Public Health, University of Saskatchewan, Saskatoon, SK, Canada
- Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada
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15
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O'Shea SA, Shih LC. Global Epidemiology of Movement Disorders: Rare or Underdiagnosed? Semin Neurol 2023; 43:4-16. [PMID: 36893797 DOI: 10.1055/s-0043-1764140] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/11/2023]
Abstract
In this manuscript, we review the epidemiology of movement disorders including Parkinson's disease (PD), atypical parkinsonism, essential tremor, dystonia, functional movement disorders, tic disorders, chorea, and ataxias. We emphasize age-, sex-, and geography-based incidence and prevalence, as well as notable trends including the rising incidence and prevalence of PD. Given the growing global interest in refining clinical diagnostic skills in recognizing movement disorders, we highlight some key epidemiological findings that may be of interest to clinicians and health systems tasked with diagnosing and managing the health of patients with movement disorders.
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Affiliation(s)
- Sarah A O'Shea
- Department of Neurology, Columbia University, Vagelos College of Physicians and Surgeons, New York City, New York
| | - Ludy C Shih
- Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.,Department of Neurology, Boston Medical Center, Boston, Massachusetts
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16
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Lacroix R, Kurrasch DM. Glyphosate Toxicity: In Vivo, In Vitro, and Epidemiological Evidence. Toxicol Sci 2023; 192:kfad018. [PMID: 36857578 DOI: 10.1093/toxsci/kfad018] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/03/2023] Open
Abstract
Glyphosate is the most applied agricultural chemical worldwide and has become nearly ubiquitous throughout the environment. Glyphosate is an effective herbicide because it disrupts the shikimate pathway, which is responsible for the synthesis of essential amino acids in plants and microorganisms. Given that there is no known target for glyphosate in higher animals, its toxicity to humans and other animals is heavily debated, especially after the 2015 IARC ruling that glyphosate is carcinogenic. Today, a growing body of literature shows in vitro, in vivo, and epidemiological evidence for the toxicity of glyphosate across animal species. With the application of glyphosate increasing globally, it is important to discuss these reports to enable a broader conversation on glyphosate toxicity and its impact on human and environmental health. Here, we summarize the recent glyphosate literature and discuss its implications.
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Affiliation(s)
- Rachel Lacroix
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
| | - Deborah M Kurrasch
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Alberta Children's Hospital Research Institute (ACHRI), Calgary, AB, Canada
- Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
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17
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Seo MH, Yeo S. Association Between Decreased Srpk3 Expression and Increased Substantia Nigra Alpha-Synuclein Level in an MPTP-Induced Parkinson's Disease Mouse Model. Mol Neurobiol 2023; 60:780-788. [PMID: 36369636 DOI: 10.1007/s12035-022-03104-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 10/25/2022] [Indexed: 11/13/2022]
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder and is caused by the loss of dopaminergic neurons in the substantia nigra (SN). However, the reason for the death of dopaminergic neurons remains unclear. An increase in α-synuclein (α-syn) expression is an important factor in the pathogenesis of PD. In the current study, we investigated the association between serine/arginine-rich protein-specific kinase 3 (Srpk3) and PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and in SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). Srpk3 expression was significantly downregulated, while tyrosine hydroxylase (TH) expression decreased and α-syn expression increased after 4 weeks of MPTP treatment. Dopaminergic cell reduction and α-syn expression increase were demonstrated by Srpk3 expression inhibition by siRNA in SH-SY5Y cells. Moreover, a decrease in Srpk3 expression upon siRNA treatment promoted dopaminergic cell reduction and α-syn expression increase in SH-SY5Y cells treated with MPP+ . These results suggested that Srpk3 expression decrease due to Srpk3 siRNA caused both TH level decrease and α-syn expression increase. This raises new possibilities for studying how Srpk3 controls dopaminergic cells and α-syn expression, which may be related to PD pathogenesis. Our results provide an avenue for understanding the role of Srpk3 in dopaminergic cell loss and α-syn upregulation in SN. Furthermore, this study supports a therapeutic possibility for PD in that the maintenance of Srpk3 expression inhibits dopaminergic cell reduction.
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Affiliation(s)
- Min Hyung Seo
- Department of Meridian and Acupoint, College of Korean Medicine, Sangji University, #83 Sangjidae-Gil, Wonju, 26339, Gangwon-Do, Republic of Korea
| | - Sujung Yeo
- Department of Meridian and Acupoint, College of Korean Medicine, Sangji University, #83 Sangjidae-Gil, Wonju, 26339, Gangwon-Do, Republic of Korea. .,Research Institute of Korean Medicine, Sangji University, Wonju, 26339, Republic of Korea.
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18
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Chang ET, Odo NU, Acquavella JF. Systematic literature review of the epidemiology of glyphosate and neurological outcomes. Int Arch Occup Environ Health 2023; 96:1-26. [PMID: 35604441 PMCID: PMC9823069 DOI: 10.1007/s00420-022-01878-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/26/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE Human health risk assessments of glyphosate have focused on animal toxicology data for determining neurotoxic potential. Human epidemiological studies have not yet been systematically reviewed for glyphosate neurotoxicity hazard identification. The objective of this systematic literature review was to summarize the available epidemiology of glyphosate exposure and neurological outcomes in humans. METHODS As of December 2021, 25 eligible epidemiological studies of glyphosate exposure and neurological endpoints were identified and assessed for five quality dimensions using guidance from the U.S. Environmental Protection Agency. Studies that assessed personal use of glyphosate were prioritized, whereas those assessing indirect exposure (other than personal use) were rated as low quality, since biomonitoring data indicate that indirect metrics of glyphosate exposure almost always equate to non-detectable glyphosate doses. RESULTS Overall, the scientific evidence on glyphosate and neurotoxicity in humans is sparse and methodologically limited, based on nine included epidemiological studies of neurodegenerative outcomes (two high quality), five studies of neurobehavioral outcomes (two high quality), six studies of neurodevelopmental outcomes (none high quality), and five studies of other and mixed neurological outcomes (one high quality). The five high-quality studies showed no association between glyphosate use and risk of depression, Parkinson disease, or peripheral nerve conduction velocity. Results were mixed among the eight moderate-quality studies, which did not demonstrate consistent associations with any neurological endpoints or categories. Low-quality studies were considered uninformative about possible neurotoxic effects due primarily to questionable assessments of indirect exposure. CONCLUSIONS No association has been demonstrated between glyphosate and any neurological outcomes in humans. To move the state of science forward, epidemiological studies should focus on scenarios involving direct and frequent use of glyphosate while collecting information on validated health outcomes, concomitant agricultural exposures, and relevant personal characteristics.
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Affiliation(s)
- Ellen T Chang
- Center for Health Sciences, Exponent, Inc., 149 Commonwealth Dr, Menlo Park, CA, 94025, USA.
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
| | - Nnaemeka U Odo
- Center for Health Sciences, Exponent, Inc., Oakland, CA, USA
| | - John F Acquavella
- Department of Clinical Epidemiology, University of Aarhus, Aarhus, Denmark
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19
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Mitchell E, Chohan H, Bestwick JP, Noyce AJ. Alcohol and Parkinson's Disease: A Systematic Review and Meta-Analysis. JOURNAL OF PARKINSON'S DISEASE 2022; 12:2369-2381. [PMID: 36442208 DOI: 10.3233/jpd-223522] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND A substantial body of research has examined the relationship between alcohol consumption and risk of Parkinson's disease (PD). OBJECTIVE To provide an updated systematic review and meta-analysis of observational studies examining the relationship between alcohol consumption and risk of PD. METHODS Eligible studies comparing PD risk in ever vs. never alcohol drinkers were sourced from six databases. Outcomes were pooled using standard meta-analysis techniques. Separate female and male estimates were generated from studies reporting sex-specific data. Additionally, cohort studies stratifying participants by quantity of alcohol intake were integrated in a dose-response analysis. RESULTS 52 studies were included, totaling 63,707 PD patients and 9,817,924 controls. Our meta-analysis supported a statistically significant overrepresentation of never drinkers among PD subjects; odds ratio (OR) for ever drinking alcohol 0.84 (95% confidence interval (CI) 0.76 - 0.92). A subgroup analysis revealed similar effect estimates in females and males. A further synthesis of seven cohort studies suggested a negative, dose-dependent association between alcohol and risk of PD. CONCLUSION In the absence of a known neuroprotective pathway, there may be reason to doubt a true biological effect. The role of survivor bias, selection and recall bias, misclassification, and residual confounding requires consideration. Alternatively, observations might be attributable to reverse causation if those predestined for PD alter their alcohol habits during the preclinical phase. Major limitations of our study include high between-study heterogeneity (I2 = 93.2%) and lack of adjustment for key confounders, namely smoking status.
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Affiliation(s)
- Eleanor Mitchell
- Preventive Neurology Unit, Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK
| | - Harneek Chohan
- Preventive Neurology Unit, Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK
| | - Jonathan P Bestwick
- Preventive Neurology Unit, Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK
| | - Alastair J Noyce
- Preventive Neurology Unit, Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK
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20
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Abstract
Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.
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21
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McGwin G, Griffin RL. An ecological study regarding the association between paraquat exposure and end stage renal disease. Environ Health 2022; 21:127. [PMID: 36503540 PMCID: PMC9743741 DOI: 10.1186/s12940-022-00946-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 12/01/2022] [Indexed: 05/09/2023]
Abstract
BACKGROUND Persons who experience paraquat poisoning rapidly develop damage to a variety of organ systems including acute kidney injury (AKI), the occurrence of which is associated with an increased risk of death. However, little is known about the effects of chronic paraquat exposure on renal function and the onset of chronic renal disease. The objective of the current study is to assess the association between paraquat exposure and the incidence of end stage renal disease (ESRD) in the United States. METHODS Data on the incidence of ESRD for the period 2010 through 2017 and kilograms of paraquat use per square mile for each county in the conterminous United States was obtained from the United States Renal Data System (USRDS) and the National Water Quality Assessment (NAWQA) Program, respectively. Negative binomial regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association between quartiles of paraquat exposure and the incidence of ESRD. RESULTS The incidence of ESRD increased with increasing paraquat density. Based on a 20-year exposure lag, those in the highest paraquat density quartile had a 21% higher rate of ESRD compared to the lowest quartile whereas for a 15-year lag the increase was 26%. Adjusted associations were attenuated though still followed an increasing linear trend across quintiles. CONCLUSIONS The results of this study are consistent with a large number of studies documenting a high incidence of AKI and a small number of studies chronic renal disease following acute and chronic paraquat exposure, respectively. While the pathophysiological mechanisms underlying kidney injury following paraquat poisoning are well understood, more research is necessary to understand the natural history of chronic kidney disease due to chronic paraquat exposure.
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Affiliation(s)
- Gerald McGwin
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 700 South 18th Street, Suite 609, Birmingham, AL, 35294-0009, USA.
| | - Russell L Griffin
- Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 700 South 18th Street, Suite 609, Birmingham, AL, 35294-0009, USA
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22
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Arab A, Mostafalou S. Neurotoxicity of pesticides in the context of CNS chronic diseases. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2022; 32:2718-2755. [PMID: 34663153 DOI: 10.1080/09603123.2021.1987396] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 09/26/2021] [Indexed: 06/13/2023]
Abstract
Following the introduction and application of pesticides in human life, they have always been along with health concerns both in acute poisoning and chronic toxicities. Neurotoxicity of pesticides in chronic exposures has been known as one of the most important human health problems, as most of these chemicals act through interacting with some elements of nervous system. Pesticide-induced neurotoxicity can be defined in different categories of neurological disorders including neurodegenerative (Alzheimer, Parkinson, amyotrophic lateral sclerosis, multiple sclerosis), neurodevelopmental (attention deficit hyperactivity disorder, autism spectrum disorders, developmental delay, and intellectual disability), neurobehavioral and neuropsychiatric (depression/suicide attempt, anxiety/insomnia, and cognitive impairment) disorders some of which are among the most debilitating human health problems. In this review, neurotoxicity of pesticides in the mentioned categories and sub-categories of neurological diseases have been systematically presented in relation to different route of exposures including general, occupational, environmental, prenatal, postnatal, and paternal.
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Affiliation(s)
- Ali Arab
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Sara Mostafalou
- Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran
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23
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Paul KC, Ritz B. Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson's disease. ENVIRONMENT INTERNATIONAL 2022; 170:107613. [PMID: 36395557 PMCID: PMC9897493 DOI: 10.1016/j.envint.2022.107613] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 10/09/2022] [Accepted: 11/01/2022] [Indexed: 06/01/2023]
Abstract
BACKGROUND Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson's disease (PD). OBJECTIVES Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. METHODS We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. RESULTS Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. CONCLUSIONS Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology.
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Affiliation(s)
- Kimberly C Paul
- Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA.
| | - Beate Ritz
- Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA
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24
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Vellingiri B, Chandrasekhar M, Sri Sabari S, Gopalakrishnan AV, Narayanasamy A, Venkatesan D, Iyer M, Kesari K, Dey A. Neurotoxicity of pesticides - A link to neurodegeneration. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 243:113972. [PMID: 36029574 DOI: 10.1016/j.ecoenv.2022.113972] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 08/10/2022] [Accepted: 08/11/2022] [Indexed: 05/15/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder which mainly targets motor symptoms such as tremor, rigidity, bradykinesia and postural instability. The physiological changes occur due to dopamine depletion in basal ganglia region of the brain. PD aetiology is not yet elucidated clearly but genetic and environmental factors play a prominent role in disease occurrence. Despite of various environmental factors, pesticides exposure has been convicted as major candidate in PD pathogenesis. Among various pesticides 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely investigated in PD following with paraquat (PQ), maneb (MB), organochlorines (OC) and rotenone. Effect of these pesticides has been suggested to be involved in oxidative stress, alterations in dopamine transporters, mitochondrial dysfunction, α-synuclein (αSyn) fibrillation, and neuroinflammation in PD. The present review discusses the influence of pesticides in neurodegeneration and its related epidemiological studies conducted in PD. Furthermore, we have deliberated the common pesticides involved in PD and its associated genetic alterations and the probable mechanism of them behind PD pathogenesis. Hence, we conclude that pesticides play a prominent role in PD pathogenesis and advance research is needed to investigate the alterations in genetic and mechanistic aspects of PD.
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Affiliation(s)
- Balachandar Vellingiri
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.
| | - Mamatha Chandrasekhar
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641046, Tamil Nadu, India
| | - S Sri Sabari
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641046, Tamil Nadu, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Arul Narayanasamy
- Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore 641046, Tamil Nadu, India
| | - Dhivya Venkatesan
- Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore 641046, Tamil Nadu, India
| | - Mahalaxmi Iyer
- Livestock Farming and Bioresource Technology, Tamil Nadu, India
| | - Kavindra Kesari
- Department of Applied Physics, School of Science, Aalto University, Espoo, 00076, Finland.
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata, 700073, West Bengal, India
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25
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Abstract
Exposure to organophosphorus pesticides (OP) can have chronic adverse effects that are independent of inhibition of acetylcholinesterase, the classic target for acute OP toxicity. In pure proteins, the organophosphorus pesticide chlorpyrifos oxon induces a cross-link between lysine and glutamate (or aspartate) with loss of water. Tubulin is particularly sensitive to OP-induced cross-linking. Our goal was to explore OP-induced cross-linking in a complex protein sample, MAP-rich tubulin from Sus scrofa and to test 8 OP for their capacity to promote isopeptide cross-linking. We treated 100 μg of MAP-rich tubulin with 100 μM chlorpyrifos, chlorpyrifos oxon, methamidophos, paraoxon, diazinon, diazoxon, monocrotophos, or dichlorvos. Each sample was separated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and stained with Coomassie blue. Five gel slices (at about 30, 50, 150, and 300 kDa, and the top of the separating gel) were removed from the lanes for each of the eight OP samples and from untreated control lanes. These gel slices were subjected to in-gel trypsin digestion. MSMS fragmentation spectra of the tryptic peptides were examined for isopeptide cross-links. Sixteen spectra yielded convincing evidence for isopeptide cross-linked peptides. Ten were from the chlorpyrifos oxon reaction, 1 from dichlorvos, 1 from paraoxon, 1 from diazinon, and 3 from diazoxon. It was concluded that catalysis of protein cross-linking is a general property of organophosphorus pesticides and pesticide metabolites. Data are available via ProteomeXchange with identifier PXD034529.
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Affiliation(s)
- Lawrence M Schopfer
- Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
| | - Seda Onder
- Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.,Department of Biochemistry, School of Pharmacy, Hacettepe University, Ankara 06100, Turkey
| | - Oksana Lockridge
- Eppley Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States
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26
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Naraine AS, Aker R, Sweeney I, Kalvey M, Surtel A, Shanbhag V, Dawson-Scully K. Roundup and glyphosate's impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans. Sci Rep 2022; 12:13655. [PMID: 35999230 PMCID: PMC9399239 DOI: 10.1038/s41598-022-17537-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/27/2022] [Indexed: 11/28/2022] Open
Abstract
As 3 billion pounds of herbicides are sprayed over farmlands every year, it is essential to advance our understanding how pesticides may influence neurological health and physiology of both humans and other animals. Studies are often one-dimensional as the majority examine glyphosate by itself. Farmers and the public use commercial products, like Roundup, containing a myriad of chemicals in addition to glyphosate. Currently, there are no neurological targets proposed for glyphosate and little comparison to Roundup. To investigate this, we compared how glyphosate and Roundup affect convulsant behavior in C.elegans and found that glyphosate and Roundup increased seizure-like behavior. Key to our initial hypothesis, we found that treatment with an antiepileptic drug rescued the prolonged convulsions. We also discovered over a third of nematodes exposed to Roundup did not recover from their convulsions, but drug treatment resulted in full recovery. Notably, these effects were found at concentrations that are 1,000-fold dilutions of previous findings of neurotoxicity, using over 300-fold less herbicide than the lowest concentration recommended for consumer use. Exploring mechanisms behind our observations, we found significant evidence that glyphosate targets GABA-A receptors. Pharmacological experiments which paired subeffective dosages of glyphosate and a GABA-A antagonist yielded a 24% increase in non-recovery compared to the antagonist alone. GABA mutant strain experiments showed no effect in a GABA-A depleted strain, but a significant, increased effect in a glutamic acid decarboxylase depleted strain. Our findings characterize glyphosate’s exacerbation of convulsions and propose the GABA-A receptor as a neurological target for the observed physiological changes. It also highlights glyphosate’s potential to dysregulate inhibitory neurological circuits.
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Affiliation(s)
- Akshay S Naraine
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL, USA. .,IMPRS for Synapses and Circuits, Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
| | - Rebecca Aker
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL, USA
| | - Isis Sweeney
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL, USA
| | - Meghan Kalvey
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL, USA
| | - Alexis Surtel
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL, USA
| | - Venkatesh Shanbhag
- Department of Chemistry and Physics, Halmos College of Arts and Sciences, Nova Southeastern University, Davie, FL, USA
| | - Ken Dawson-Scully
- Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL, USA.,Department of Psychology and Neuroscience, College of Psychology, Nova Southeastern University, Davie, FL, USA
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27
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Rocha SM, Bantle CM, Aboellail T, Chatterjee D, Smeyne RJ, Tjalkens RB. Rotenone induces regionally distinct α-synuclein protein aggregation and activation of glia prior to loss of dopaminergic neurons in C57Bl/6 mice. Neurobiol Dis 2022; 167:105685. [PMID: 35257879 PMCID: PMC9615439 DOI: 10.1016/j.nbd.2022.105685] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/14/2022] [Accepted: 03/02/2022] [Indexed: 12/21/2022] Open
Abstract
Rotenone is a naturally occurring insecticide that inhibits mitochondrial complex I and leads to neurochemical and neuropathological deficits closely resembling those in Parkinson's disease (PD). Deficits include loss of dopaminergic neurons (DAn) in the substantia nigra pars compacta (SNpc), decreased dopamine levels and aggregation of misfolded alpha-synuclein (p129). In rat models of rotenone-induced parkinsonism, the progression of neuronal injury has been associated with activation of microglia and astrocytes. However, these neuroinflammatory changes have been challenging to study in mice, in part because the systemic rotenone exposure model utilized in rats is more toxic to mice. To establish a reproducible murine model of rotenone-induced PD, we therefore investigated the progression of neuroinflammation, protein aggregation and DAn loss in C57Bl/6 mice by exposing animals to 2.5 mg/kg/day rotenone for 14 days, followed by a two-week period where neuroinflammation is allowed to progress. Our results indicate that initial cellular dysfunction leads to increased formation of proteinase K-resistant p129 aggregates in the caudate-putamen and SNpc. Clearance of these aggregates was region- and cell type-specific, with the early appearance of reactive astrocytes coinciding with accumulation of p129 in the SNpc. Phagocytic microglial cells containing p129 aggregates were observed proximal to p129+ DAn in the SNpc. The majority of neuronal loss in the SNpc occurred during the two-week period after rotenone exposure, subsequent to the peak of microglia and astrocyte activation, as well as the peak of p129 aggregation. A secondary peak of p129 coincided with neurodegeneration at later timepoints. These data indicate that systemic exposure to rotenone in C57Bl/6 mice causes progressive accumulation and regional spread of p129 aggregates that precede maximal loss of DAn. Thus, activation of glial cells and aggregation of p129 appear to drive neuronal loss following neurotoxic stress imposed by exposure to rotenone.
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Affiliation(s)
- Savannah M Rocha
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, United States of America; Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, United States of America
| | - Collin M Bantle
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, United States of America
| | - Tawfik Aboellail
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, United States of America
| | - Debotri Chatterjee
- Jefferson Comprehensive Parkinson's Center, Vickie & Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, United States of America
| | - Richard J Smeyne
- Jefferson Comprehensive Parkinson's Center, Vickie & Jack Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, PA 19107, United States of America
| | - Ronald B Tjalkens
- Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, United States of America.
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28
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Moser VC, Morris-Schaffer K, Richardson JR, Li AA. Glyphosate and neurological outcomes: A systematic literature review of animal studies. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2022; 25:162-209. [PMID: 35676826 DOI: 10.1080/10937404.2022.2083739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Studies of nervous system effects of glyphosate, a widely used herbicide, have not been critically examined. The aim of this paper was to systematically review glyphosate-induced neurotoxicity literature to determine its usefulness in regulatory decision-making. The review was restricted to mammalian studies of behavior, neuropathology, and neuropharmacology; in vitro and other biochemical studies were considered supplementary information. Glyphosate formulation studies were also considered, despite uncertainties regarding toxicities of the formulated products; no studies used a formulation vehicle as the control. Inclusion criteria were developed a priori to ensure consistent evaluation of studies, and in vivo investigations were also ranked using ToxRTool software to determine reliability. There were 27 in vivo studies (open literature and available regulatory reports), but 11 studies were considered unreliable (mostly due to critical methodological deficiencies). There were only seven acceptable investigations on glyphosate alone. Studies differed in terms of dosing scenarios, experimental designs, test species, and commercial product. Limitations included using only one dose and/or one test time, small sample sizes, limited data presentation, and/or overtly toxic doses. While motor activity was the most consistently affected endpoint (10 of 12 studies), there were considerable differences in outcomes. In six investigations, there were no marked neuropathological changes in the central or peripheral nervous system. Other neurological effects were less consistent, and some outcomes were less convincing due to influences including high variability and small effect sizes. Taken together, these studies do not demonstrate a consistent impact of glyphosate on the structure or function of the mammalian nervous system.
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Affiliation(s)
| | - Keith Morris-Schaffer
- Exponent Inc, Center for Chemical Regulation and Food Safety, Sacramento, California
| | - Jason R Richardson
- Department of Environmental Health Sciences, Robert Stempel School of Public Health and Social Work, Florida International University, Miami, FL, United States
| | - Abby A Li
- Exponent Inc, Center for Health Sciences, Oakland, CA, United States
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29
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See WZC, Naidu R, Tang KS. Cellular and Molecular Events Leading to Paraquat-Induced Apoptosis: Mechanistic Insights into Parkinson’s Disease Pathophysiology. Mol Neurobiol 2022; 59:3353-3369. [PMID: 35306641 PMCID: PMC9148284 DOI: 10.1007/s12035-022-02799-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 03/09/2022] [Indexed: 12/17/2022]
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal features of tremor, bradykinesia, rigidity, and postural instability, in addition to other non-motor symptoms. Pathologically, PD is attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta, with the hallmark of the presence of intracellular protein aggregates of α-synuclein in the form of Lewy bodies. The pathogenesis of PD is still yet to be fully elucidated due to the multifactorial nature of the disease. However, a myriad of studies has indicated several intracellular events in triggering apoptotic neuronal cell death in PD. These include oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, alteration in dopamine catabolism, inactivation of tyrosine hydroxylase, and decreased levels of neurotrophic factors. Laboratory studies using the herbicide paraquat in different in vitro and in vivo models have demonstrated the induction of many PD pathological features. The selective neurotoxicity induced by paraquat has brought a new dawn in our perspectives about the pathophysiology of PD. Epidemiological data have suggested an increased risk of developing PD in the human population exposed to paraquat for a long term. This model has opened new frontiers in the quest for new therapeutic targets for PD. The purpose of this review is to synthesize the relationship between the exposure of paraquat and the pathogenesis of PD in in vitro and in vivo models.
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Affiliation(s)
- Wesley Zhi Chung See
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, 47500, Bandar Sunway, Selangor, Malaysia
| | - Rakesh Naidu
- Jeffrey Cheah School of Medicine and Health Science, Monash University Malaysia, 47500, Bandar Sunway, Selangor, Malaysia
| | - Kim San Tang
- School of Pharmacy, Monash University Malaysia, 47500, Bandar Sunway, Selangor, Malaysia.
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30
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Roe K. An Alternative Explanation for Alzheimer's Disease and Parkinson's Disease Initiation from Specific Antibiotics, Gut Microbiota Dysbiosis and Neurotoxins. Neurochem Res 2022; 47:517-530. [PMID: 34669122 DOI: 10.1007/s11064-021-03467-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/09/2021] [Accepted: 10/11/2021] [Indexed: 01/03/2023]
Abstract
The late onset neuropathologies, including Alzheimer's disease and Parkinson's disease, have become increasingly prevalent. Their causation has been linked to genetics, gut microbiota dysbiosis (gut dysbiosis), autoimmune diseases, pathogens and exposures to neurotoxins. An alternative explanatory hypothesis is provided for their pathogenesis. Virtually everyone has pervasive daily exposures to neurotoxins, through inhalation, skin contact, direct blood transmission and through the gastrointestinal tract by ingestion. As a result, every individual has substantial and fluctuating neurotoxin blood levels. Two major barriers to neurotoxin entry into the central nervous system are the blood-brain barrier and the intestinal wall, in the absence of gut dysbiosis. Inflammation from gut dysbiosis, induced by antibiotic usage, can increase the intestinal wall permeability for neurotoxins to reach the bloodstream, and also increase the blood-brain barrier permeability to neurotoxins. Gut dysbiosis, including gut dysbiosis caused by antibiotic treatments, is an especially high risk for neurotoxin entry into the brain to cause late onset neuropathologies. Gut dysbiosis has far-reaching immune system and central nervous system effects, and even a transient gut dysbiosis can act in combination with neurotoxins, such as aluminum, mercury, lead, arsenic, cadmium, selenium, manganese, organophosphate pesticides and organochlorines, to reach neurotoxin blood levels that can initiate a late onset neuropathology, depending on an individual's age and genetic vulnerability.
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31
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Hamdaoui Q, Zekri Y, Richard S, Aubert D, Guyot R, Markossian S, Gauthier K, Gaie-Levrel F, Bencsik A, Flamant F. Prenatal exposure to paraquat and nanoscaled TiO 2 aerosols alters the gene expression of the developing brain. CHEMOSPHERE 2022; 287:132253. [PMID: 34543901 DOI: 10.1016/j.chemosphere.2021.132253] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 09/03/2021] [Accepted: 09/13/2021] [Indexed: 06/13/2023]
Abstract
Nanopesticides are innovative pesticides involving engineered nanomaterials in their formulation to increase the efficiency of plant protection products, while mitigating their environmental impact. Despite the predicted growth of the nanopesticide use, no data is available on their inhalation toxicity and the potential cocktail effects between their components. In particular, the neurodevelopmental toxicity caused by prenatal exposures might have long lasting consequences. In the present study, we repeatedly exposed gestating mice in a whole-body exposure chamber to three aerosols, involving the paraquat herbicide, nanoscaled titanium dioxide particles (nTiO2), or a mixture of both. Particle number concentrations and total mass concentrations were followed to enable a metrological follow-up of the exposure sessions. Based on the aerosols characteristics, the alveolar deposited dose in mice was then estimated. RNA-seq was used to highlight dysregulations in the striatum of pups in response to the in utero exposure. Modifications in gene expression were identified at post-natal day 14, which might reflect neurodevelopmental alterations in this key brain area. The data suggest an alteration in the mitochondrial function following paraquat exposure, which is reminiscent of the pathological process leading to Parkinson disease. Markers of different cell lineages were dysregulated, showing effects, which were not limited to dopaminergic neurons. Exposure to the nTiO2 aerosol modulated the regulation of cytokines and neurotransmitters pathways, perhaps reflecting a minor neuroinflammation. No synergy was found between paraquat and nTiO2. Instead, the neurodevelopmental effects were surprisingly lower than the one measured for each substance separately.
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Affiliation(s)
- Quentin Hamdaoui
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France; Laboratoire National de Métrologie et D'essais (LNE), Paris, France
| | - Yanis Zekri
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France
| | - Sabine Richard
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France
| | - Denise Aubert
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France
| | - Romain Guyot
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France
| | - Suzy Markossian
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France
| | - Karine Gauthier
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France
| | | | - Anna Bencsik
- Université Claude Bernard Lyon 1, ANSES, Laboratoire de Lyon, France
| | - Frédéric Flamant
- IGFL, Functional Genomics of Thyroid Hormone Signaling Group, Lyon, France.
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32
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Parkinson's disease in a worker exposed to insecticides at a greenhouse. Ann Occup Environ Med 2021; 33:e6. [PMID: 34754467 PMCID: PMC7952772 DOI: 10.35371/aoem.2021.33.e6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 01/13/2021] [Indexed: 12/11/2022] Open
Abstract
Background Parkinson's disease (PD) is a rare, neurodegenerative disease with various occupational and environmental risk factors. Exposure to specific pesticides contributes significantly to the incidence of PD. However, it is difficult to measure the level of pesticide exposure in workers. This study presents the first case recognized the work-relatedness between PD and pesticide exposure. Case presentation A 68-year-old male was diagnosed with PD after working with pesticides at a tomato greenhouse for 12 years and 5 months. From the results of a field study, it was reasonable to assume that the patient had been exposed to a significant level of various insecticides. In the present report, we described the first accepted case of work-relatedness between PD and exposure to pesticides. The evaluation was conducted using the following steps: we ruled out other possible risk factors including additional occupational history and personal risk factors, we assessed the work environment, surveyed possible exposures, found proper epidemiological evidence, and calculated the probability of causation. The work-relatedness was determined through the review of epidemiological evidence and estimation of exposure situation and level, and biological plausibility. We also decided work-relatedness based on the exposure of PD related pesticides with identified biologically plausible and the presumption that the exposure level would be high due to the working process. Conclusions In this case, the field study and epidemiological results supported the work-relatedness of PD and exposure to pesticides. Moreover, the results of previous studies have confirmed a causal relationship between exposure to pesticides and PD.
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33
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De Miranda BR, Goldman SM, Miller GW, Greenamyre JT, Dorsey ER. Preventing Parkinson's Disease: An Environmental Agenda. JOURNAL OF PARKINSONS DISEASE 2021; 12:45-68. [PMID: 34719434 PMCID: PMC8842749 DOI: 10.3233/jpd-212922] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Fueled by aging populations and continued environmental contamination, the global burden of Parkinson's disease (PD) is increasing. The disease, or more appropriately diseases, have multiple environmental and genetic influences but no approved disease modifying therapy. Additionally, efforts to prevent this debilitating disease have been limited. As numerous environmental contaminants (e.g., pesticides, metals, industrial chemicals) are implicated in PD, disease prevention is possible. To reduce the burden of PD, we have compiled preclinical and clinical research priorities that highlight both disease prediction and primary prevention. Though not exhaustive, the "PD prevention agenda" builds upon many years of research by our colleagues and proposes next steps through the lens of modifiable risk factors. The agenda identifies ten specific areas of further inquiry and considers the funding and policy changes that will be necessary to help prevent the world's fastest growing brain disease.
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Affiliation(s)
- Briana R De Miranda
- Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama atBirmingham, Birmingham, AL, USA
| | - Samuel M Goldman
- Division of Occupational and Environmental Medicine, San Francisco VeteransAffairs Health Care System, School of Medicine, University ofCalifornia-San Francisco, San Francisco, CA, USA
| | - Gary W Miller
- Department of Environmnetal Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - J Timothy Greenamyre
- Pittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Universityof Pittsburgh, Pittsburgh, PA, USA
| | - E Ray Dorsey
- Center for Health+Technology and Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA
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34
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Pirooznia SK, Rosenthal LS, Dawson VL, Dawson TM. Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection. Pharmacol Rev 2021; 73:33-97. [PMID: 34663684 DOI: 10.1124/pharmrev.120.000189] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Parkinson disease (PD) used to be considered a nongenetic condition. However, the identification of several autosomal dominant and recessive mutations linked to monogenic PD has changed this view. Clinically manifest PD is then thought to occur through a complex interplay between genetic mutations, many of which have incomplete penetrance, and environmental factors, both neuroprotective and increasing susceptibility, which variably interact to reach a threshold over which PD becomes clinically manifested. Functional studies of PD gene products have identified many cellular and molecular pathways, providing crucial insights into the nature and causes of PD. PD originates from multiple causes and a range of pathogenic processes at play, ultimately culminating in nigral dopaminergic loss and motor dysfunction. An in-depth understanding of these complex and possibly convergent pathways will pave the way for therapeutic approaches to alleviate the disease symptoms and neuroprotective strategies to prevent disease manifestations. This review is aimed at providing a comprehensive understanding of advances made in PD research based on leveraging genetic insights into the pathogenesis of PD. It further discusses novel perspectives to facilitate identification of critical molecular pathways that are central to neurodegeneration that hold the potential to develop neuroprotective and/or neurorestorative therapeutic strategies for PD. SIGNIFICANCE STATEMENT: A comprehensive review of PD pathophysiology is provided on the complex interplay of genetic and environmental factors and biologic processes that contribute to PD pathogenesis. This knowledge identifies new targets that could be leveraged into disease-modifying therapies to prevent or slow neurodegeneration in PD.
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Affiliation(s)
- Sheila K Pirooznia
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
| | - Liana S Rosenthal
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
| | - Valina L Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
| | - Ted M Dawson
- Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering (S.K.P., V.L.D., T.M.D.), Departments of Neurology (S.K.P., L.S.R., V.L.D., T.M.D.), Departments of Physiology (V.L.D.), Solomon H. Snyder Department of Neuroscience (V.L.D., T.M.D.), Department of Pharmacology and Molecular Sciences (T.M.D.), Johns Hopkins University School of Medicine, Baltimore, Maryland; Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.); and Diana Helis Henry Medical Research Foundation, New Orleans, Louisiana (S.K.P., V.L.D., T.M.D.)
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Russo M, Humes ST, Figueroa AM, Tagmount A, Zhang P, Loguinov A, Lednicky JA, Sabo-Attwood T, Vulpe CD, Liu B. Organochlorine Pesticide Dieldrin Suppresses Cellular Interferon-Related Antiviral Gene Expression. Toxicol Sci 2021; 182:260-274. [PMID: 34051100 DOI: 10.1093/toxsci/kfab064] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Organochlorine pesticides (OCPs) are persistent pollutants linked to diverse adverse health outcomes. Environmental exposure to OCPs has been suggested to negatively impact the immune system but their effects on cellular antiviral responses remain unknown. Transcriptomic analysis of N27 rat dopaminergic neuronal cells unexpectedly detected high level expression of genes in the interferon (IFN)-related antiviral response pathways including the IFN-induced protein with tetratricopeptide repeats 1 and 2 (Ifit1/2) and the MX Dynamin Like GTPases Mx1 and Mx2. Interestingly, treatment of N27 cells with dieldrin markedly downregulated the expression of many of these genes. Dieldrin exterted a similar effect in inhibiting IFIT2 and MX1 gene expression in human SH-SY5Y neuronal cells induced by an RNA viral mimic, polyinosinic: polycytidylic acid (poly I:C) and IFIT2/3 gene expression in human pulmonary epithelial cells exposed to human influenza H1N1 virus. Mechanistically, dieldrin induced a rapid rise in levels of intracellular reactive oxygen species (iROS) and a decrease in intracellular glutathione (GSH) levels in SH-SY5Y cells. Treatment with N-acetylcysteine, an antioxidant and GSH biosynthesis precursor, effectively blocked both dieldrin-induced increases in iROS and its inhibition of poly I:C-induced upregulation of IFIT and MX gene expression, suggesting a role for intracellular oxidative status in dieldrin's modulation of antiviral gene expression. This study demonstrates that dieldrin modulates key genes of the cellular innate immune responses that are normally involved in the host's cellular defense against viral infections. Our findings have potential relevance to understanding the organismal effects of environmentally persistent organochlorine contaminants on the mammalian cellular immune system.
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Affiliation(s)
- Max Russo
- Department of Pharmacodynamics, University of Florida, College of Pharmacy, Gainesville, Florida 32610, USA
| | - Sara T Humes
- Department of Environmental and Global Health, University of Florida, College of Public Health and Health Professions, Gainesville, Florida 32610, USA
| | - Ariana M Figueroa
- Department of Pharmacodynamics, University of Florida, College of Pharmacy, Gainesville, Florida 32610, USA
| | - Abderrahmane Tagmount
- Department of Physiological Sciences, University of Florida, College of Veterinary Medicine, Gainesville, Florida 32610, USA
| | - Ping Zhang
- Department of Pharmacodynamics, University of Florida, College of Pharmacy, Gainesville, Florida 32610, USA
| | - Alex Loguinov
- Department of Physiological Sciences, University of Florida, College of Veterinary Medicine, Gainesville, Florida 32610, USA
| | - John A Lednicky
- Department of Environmental and Global Health, University of Florida, College of Public Health and Health Professions, Gainesville, Florida 32610, USA
| | - Tara Sabo-Attwood
- Department of Environmental and Global Health, University of Florida, College of Public Health and Health Professions, Gainesville, Florida 32610, USA
| | - Chris D Vulpe
- Department of Physiological Sciences, University of Florida, College of Veterinary Medicine, Gainesville, Florida 32610, USA
| | - Bin Liu
- Department of Pharmacodynamics, University of Florida, College of Pharmacy, Gainesville, Florida 32610, USA
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Does paraquat cause Parkinson's disease? A review of reviews. Neurotoxicology 2021; 86:180-184. [PMID: 34400206 DOI: 10.1016/j.neuro.2021.08.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 12/26/2022]
Abstract
To examine the extent to which a consensus exists in the scientific community regarding the relationship between exposure to paraquat and Parkinson's disease, a critical review of reviews was undertaken focusing on reviews published between 2006 and the present that offered opinions on the issue of causation. Systematic searches were undertaken of scientific databases along with searches of published bibliographies to identify English language reviews on the topic of paraquat and Parkinson's disease including those on the broader topic of environmental and occupational risk factors for Parkinson's disease. Of the 269 publications identified in the searches, there were twelve reviews, some with meta-analyses, that met the inclusion criteria. Information on methods used by the reviewers, if any, and source of funding was collected; the quality of the reviews was considered. No author of any published review stated that it has been established that exposure to paraquat causes Parkinson's disease, regardless of methods used and independent of funding source. A consensus exists in the scientific community that the available evidence does not warrant a claim that paraquat causes Parkinson's disease. Future research on this topic should focus on improving the quality of epidemiological studies including better exposure measures and identifying specific mechanisms of action. Future reviews of emerging evidence should be structured as systematic narrative reviews with meta-analysis if appropriate.
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Yang H, Lin Q, Chen N, Luo Z, Zheng C, Li J, Zheng F, Guo Z, Cai P, Wu S, Wang YL, Li H. LncRNA NR_030777 Alleviates Paraquat-Induced Neurotoxicity by Regulating Zfp326 and Cpne5. Toxicol Sci 2021; 178:173-188. [PMID: 32735315 DOI: 10.1093/toxsci/kfaa121] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Paraquat (PQ) is herbicide widely used in agricultural production. It is identified as an environmental toxicant that could lead to neurodegeneration damage. Parkinson's disease (PD) is a central nervous system degenerative disease that occurs in the elderly. Main risk factors for PD include genetic and environmental variables, but its specific mechanism is still not well understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an important role in PD. LncRNA NR_030777 has a full length of 2208 bp and is highly conserved among species. RNA profiling showed a significant alteration in lncRNA NR_030777 expression upon PQ-induced neurotoxicity. However, little is known on the functional relevance of lncRNA NR_030777 in the development of PQ. In this study, we discovered a vital protective role of lncRNA NR_030777 in PQ-induced neurotoxicity. The expression of NR_030777 correlates with elevated level of reactive oxygen species induced by PQ. In addition, activated expression of NR_030777 alleviates neurotoxicity by regulating the expression of Zfp326 and Copine 5. We report that lncRNA NR_030777 has a vital protective role in neurotoxicity induced by environmental toxicants such as PQ. This study could serve as an exemplary case for lncRNAs to be considered as a potential target for the prevention and treatment of PQ-induced neurodegenerative disorders such as PD.
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Affiliation(s)
- Hongyu Yang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.,Department of Labor Hygiene and Environmental Hygiene, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Qingxia Lin
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Nengzhou Chen
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Zhousong Luo
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Chunyan Zheng
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Jing Li
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Fuli Zheng
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.,The Key Laboratory of Environment and Health
| | - Zhenkun Guo
- The Key Laboratory of Environment and Health.,Fujian Provincial Key Laboratory of Environment Factors and Cancer
| | - Ping Cai
- The Key Laboratory of Environment and Health.,Fujian Provincial Key Laboratory of Environment Factors and Cancer.,Department of Health Inspection and Quarantine
| | - Siying Wu
- Fujian Provincial Key Laboratory of Environment Factors and Cancer.,Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Yuan-Liang Wang
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.,The Key Laboratory of Environment and Health
| | - Huangyuan Li
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China.,The Key Laboratory of Environment and Health.,Fujian Provincial Key Laboratory of Environment Factors and Cancer
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Lifestyle Factors and Parkinson's Disease Risk in a Rural New England Case-Control Study. PARKINSONS DISEASE 2021; 2021:5541760. [PMID: 34306610 PMCID: PMC8270694 DOI: 10.1155/2021/5541760] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/02/2021] [Accepted: 06/25/2021] [Indexed: 12/21/2022]
Abstract
Introduction Parkinson's disease (PD) is an age-related neurodegenerative disease likely caused by complex interactions between genetic and environmental risk factors. Exposure to pesticides, toxic metals, solvents, and history of traumatic brain injury have been implicated as environmental risk factors for PD, underscoring the importance of identifying risk factors associated with PD across different communities. Methods We conducted a questionnaire-based case-control study in a rural area on the New Hampshire/Vermont border, enrolling PD patients and age- and sex-matched controls from the general population between 2017 and 2020. We assessed frequent participation in a variety of recreational and occupational activities and surveyed potential chemical exposures. Results Suffering from “head trauma or a concussion” prior to diagnosis was associated with a fourfold increased risk of PD. Adjustment for head trauma negated any risk of participation in “strenuous athletic activities.” We observed a 2.7-fold increased risk of PD associated with activities involving lead (adjusted p=0.038). Conclusion Implicating these factors in PD risk favors public health efforts in exposure mitigation while also motivating future work mechanisms and intervention opportunities.
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Venkatasamy L, Nizamutdinov D, Jenkins J, Shapiro LA. Vagus Nerve Stimulation Ameliorates Cognitive Impairment and Increased Hippocampal Astrocytes in a Mouse Model of Gulf War Illness. Neurosci Insights 2021; 16:26331055211018456. [PMID: 34104886 PMCID: PMC8165814 DOI: 10.1177/26331055211018456] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 04/29/2021] [Indexed: 01/17/2023] Open
Abstract
Gulf war illness (GWI), is a chronic multi-symptom illness that has impacted approximately one-third of the veterans who served in the 1990 to 1991 Gulf War. GWI symptoms include cognitive impairments (eg, memory and concentration problems), headaches, migraines, fatigue, gastrointestinal and respiratory issues, as well as emotional deficits. The exposure to neurological chemicals such as the anti-nerve gas drug, pyridostigmine bromide (PB), and the insecticide permethrin (PER), may contribute to the etiologically related factors of GWI. Various studies utilizing mouse models of GWI have reported the interplay of these chemical agents in increasing neuroinflammation and cognitive dysfunction. Astrocytes are involved in the secretion of neuroinflammatory cytokines and chemokines in pathological conditions and have been implicated in GWI symptomology. We hypothesized that exposure to PB and PER causes lasting changes to hippocampal astrocytes, concurrent with chronic cognitive deficits that can be reversed by cervical vagus nerve stimulation (VNS). GWI was induced in CD1 mice by injecting the mixture of PER (200 mg/kg) and PB (2 mg/kg), i.p. for 10 consecutive days. VNS stimulators were implanted at 33 weeks after GWI induction. The results show age-related cognitive alterations at approximately 9 months after exposure to PB and PER. The results also showed an increased number of GFAP-labeled astrocytes in the hippocampus and dentate gyrus that was ameliorated by VNS.
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Affiliation(s)
- Lavanya Venkatasamy
- Department of Neuroscience and Experimental Therapeutics, Texas A&M University, Bryan, TX, USA
| | - Damir Nizamutdinov
- Department of Neuroscience and Experimental Therapeutics, Texas A&M University, Bryan, TX, USA
| | - Jaclyn Jenkins
- Department of Neuroscience and Experimental Therapeutics, Texas A&M University, Bryan, TX, USA
| | - Lee A Shapiro
- Department of Neuroscience and Experimental Therapeutics, Texas A&M University, Bryan, TX, USA
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Tomenson JA, Campbell C. Mortality from Parkinson's disease and other causes among a workforce manufacturing paraquat: an updated retrospective cohort study. J Occup Med Toxicol 2021; 16:20. [PMID: 34044863 PMCID: PMC8157632 DOI: 10.1186/s12995-021-00309-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 05/19/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Epidemiological studies of the association between Parkinson's disease (PD) and paraquat (PQ) exposure have given inconsistent findings. The aim of the study was to update information on the risk of PD and mortality from major causes of death among a UK workforce who manufactured PQ by extending the follow-up by seven and a half years. METHODS This retrospective cohort study included all employees who had ever worked on any of the four plants at Widnes, UK where PQ was manufactured between 1961 and 1995. The 926 male and 42 female workers were followed through 31 December 2017. Mortalities for males were compared with national and local rates, including rates for PD as a mentioned cause of death. RESULTS A total of 394 male and 21 female workers had died by end of follow-up. Four death certificates of male workers mentioned PD, including two deaths that were due to PD. At least 6 death certificates of male employees would have been expected to have mentioned PD (SMR = 0.67; 95% CI 0.18-1.72). Reduced mortalities compared with local rates were found for major causes of death. CONCLUSIONS The study provided no evidence of an increased risk of PD, or increased mortalities from other causes among PQ production workers whose exposure to PQ on a daily basis was at least comparable to that of a PQ sprayer or mixer/loader.
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Shrestha S, Parks CG, Richards-Barber M, Chen H, Sandler DP. Parkinson's disease case ascertainment in a large prospective cohort. PLoS One 2021; 16:e0251852. [PMID: 34010345 PMCID: PMC8133399 DOI: 10.1371/journal.pone.0251852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 05/03/2021] [Indexed: 11/30/2022] Open
Abstract
Background In epidemiologic studies where physician-based case adjudication is not feasible, Parkinson’s disease (PD) case ascertainment is often limited to self-reports which may not be accurate. We evaluated strategies to identify PD cases in the Agricultural Health Study (AHS). Methods Doctor-diagnosed PD was self-reported on all cohort-wide surveys; potential cases were also identified from death certificates. Follow-up surveys asked about PD-related motor and non-motor symptoms. For PD confirmation, we collected additional diagnosis, symptom, and treatment data from 510 potential PD cases or their proxy (65% of those contacted) in a supplemental screener and obtained medical records for a subset (n = 65). We classified PD cases using established criteria and screener data. Results Of 510 potential PD cases, 75% were considered “probable” or “possible”; this proportion increased among participants diagnosed by a specialist (81.2%), taking PD medication (85.2%), or reporting ≥5 motor symptoms (86.8%) in a regular AHS survey. Of those with medical records, 93% (57 of 61) of probable or possible PD was confirmed. Never-smoking and non-motor and motor symptoms reported in prior AHS surveys were more common with probable/possible PD than unconfirmed PD. Conclusion In this retrospective PD case ascertainment effort, we found that PD self-report with information on motor symptoms or medications may be a reasonable alternative for identifying PD cases when physician exam is not feasible. Because of intervening mortality, screeners could not be obtained from about one-third of those contacted. Thus, findings warrant replication.
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Affiliation(s)
- Srishti Shrestha
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, United States of America
| | - Christine G. Parks
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, United States of America
| | | | - Honglei Chen
- Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan, United States of America
| | - Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina, United States of America
- * E-mail:
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Chen N, Guo Z, Luo Z, Zheng F, Shao W, Yu G, Cai P, Wu S, Li H. Drp1-mediated mitochondrial fission contributes to mitophagy in paraquat-induced neuronal cell damage. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 272:116413. [PMID: 33422762 DOI: 10.1016/j.envpol.2020.116413] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 12/20/2020] [Accepted: 12/29/2020] [Indexed: 06/12/2023]
Abstract
Paraquat (PQ) is one of the most widely used herbicides in the world due to its excellent weed control effects. Accumulating evidence has revealed that long-term exposure to PQ can significantly increase the risk of Parkinson's disease (PD). However, the underlying molecular mechanisms are yet to be fully understood. Hence, we investigated the potential role of reactive oxygen species (ROS) and dynamin-related protein 1 (DRP1) in PQ-induced mitophagy, aiming to elaborate on possible molecular mechanisms involved in PQ-triggered neurotoxicity. Our results showed that ROS were increased, mitochondrial membrane potential was decreased at 100, 200, and 300 μM PQ concentrations, and autophagy pathways were activated at a concentration of 100 μM in neuronal cells. In addition, excessive mitophagy was observed in neurons exposed to 300 μM PQ for 24 h. Then, ROS-mediated mitochondrial fission was found to contribute to PQ-induced excessive mitophagy. Moreover, all aforementioned changes were significantly ameliorated by mdivi-1. Thus, our findings provide a novel neurotoxic mechanism and reveal the DRP1-mitochondrial fission pathway as a potential target for treatments of PQ-induced excessive mitophagy, serving as an alternative target for the prevention and treatment of Parkinson's disease. Because harmful substances are transmitted and enriched in the food chain, the toxic effect of environmental paraquat is nonnegligible, and more investigations are needed.
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Affiliation(s)
- Nengzhou Chen
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Zhenkun Guo
- The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Zhousong Luo
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Fuli Zheng
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Wenya Shao
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Guangxia Yu
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Ping Cai
- Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Siying Wu
- The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
| | - Huangyuan Li
- Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, 350122, China; Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
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Wen S, Aki T, Unuma K, Uemura K. Chemically Induced Models of Parkinson's Disease: History and Perspectives for the Involvement of Ferroptosis. Front Cell Neurosci 2020; 14:581191. [PMID: 33424553 PMCID: PMC7786020 DOI: 10.3389/fncel.2020.581191] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 11/30/2020] [Indexed: 12/21/2022] Open
Abstract
Ferroptosis is a newly discovered form of necrotic cell death characterized by its dependency on iron and lipid peroxidation. Ferroptosis has attracted much attention recently in the area of neurodegeneration since the involvement of ferroptosis in Parkinson’s disease (PD), a major neurodegenerative disease, has been indicated using animal models. Although PD is associated with both genetic and environmental factors, sporadic forms of PD account for more than 90% of total PD. Following the importance of environmental factors, various neurotoxins are used as chemical inducers of PD both in vivo and in vitro. In contrast to other neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases (AD and HD), many of the characteristics of PD can be reproduced in vivo by the use of specific neurotoxins. Given the indication of ferroptosis in PD pathology, several studies have been conducted to examine whether ferroptosis plays role in the loss of dopaminergic neurons in PD. However, there are still few reports showing an authentic form of ferroptosis in neuronal cells during exposure to the neurotoxins used as PD inducers. In this review article, we summarize the history of the uses of chemicals to create PD models in vivo and in vitro. Besides, we also survey recent reports examining the possible involvement of ferroptosis in chemical models of PD.
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Affiliation(s)
- Shuheng Wen
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Toshihiko Aki
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kana Unuma
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Koichi Uemura
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
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Torti M, Fossati C, Casali M, De Pandis MF, Grassini P, Radicati FG, Stirpe P, Vacca L, Iavicoli I, Leso V, Ceppi M, Bruzzone M, Bonassi S, Stocchi F. Effect of family history, occupation and diet on the risk of Parkinson disease: A case-control study. PLoS One 2020; 15:e0243612. [PMID: 33332388 PMCID: PMC7746265 DOI: 10.1371/journal.pone.0243612] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 11/25/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The aetiology of Parkinson's disease (PD) is still very controversial, with a peculiar lack of established risk factors or protective behavior. METHODS We carried out a case-control study of 634 idiopathic PD patients admitted from 2011 to 2015 to two hospitals located in central Italy and 532 controls matched by hospital, gender and age (± 5 years). The study questionnaire included questions on host factors, family history, residence, occupation and lifestyle. Odds ratios (ORs) for PD and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for actual and potential confounders. RESULTS A lower OR was observed in females (0.74; 95%CI:0.58-0.96), while older age classes showed a constantly increased risk for PD (p<0.005) starting from the class 65-69 years. Subjects who reported a first degree relative affected by PD showed a borderline increase which was more evident in those enrolled in the urban center of Rome (OR = 1.65; 95%CI: 1.09-2.50). Significant reduction of the risk was associated to current smoking (OR = 0.48; 95%CI: 0.24-0.54), and to vegetables consumption (p<0.03), while borderline increases were associated to meat and cold cut consumption. Occupational activities classified according to ISCO-08 categories did not show increased risk, while higher ORs' were found for pilots and physicians. CONCLUSIONS The results from this study confirmed the higher risk of PD in males and in elderly, and the inverse association with smoking habit. The possible etiological role of familial clustering, dietary habit, and some job tasks is suggested.
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Affiliation(s)
- Margherita Torti
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
- * E-mail:
| | - Chiara Fossati
- Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, Rome, Italy
| | - Miriam Casali
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
| | | | - Paola Grassini
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
| | - Fabiana Giada Radicati
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
| | - Paola Stirpe
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
| | - Laura Vacca
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
| | - Ivo Iavicoli
- Department of Public Health University of Naples Federico II, Naples, Italy
| | - Veruscka Leso
- Department of Public Health University of Naples Federico II, Naples, Italy
| | - Marcello Ceppi
- Unit of Clinical Epidemiology, Ospedale Policlinico San Martino, Genoa, Italy
| | - Marco Bruzzone
- Unit of Clinical Epidemiology, Ospedale Policlinico San Martino, Genoa, Italy
| | - Stefano Bonassi
- Unit of Clinical and Molecular Epidemiology, Institute for Research and Medical Care, San Raffaele Pisana, Rome, Italy
- Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy
| | - Fabrizio Stocchi
- San Raffaele Pisana Institute for Research and Medical Care, Clinical Trial Center, Rome, Italy
- Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy
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Peillex C, Pelletier M. The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity. J Immunotoxicol 2020; 17:163-174. [PMID: 32897110 DOI: 10.1080/1547691x.2020.1804492] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/13/2020] [Accepted: 07/29/2020] [Indexed: 12/20/2022] Open
Abstract
Glyphosate, or N-phosphomethyl(glycine), is an organophosphorus compound and a competitive inhibitor of the shikimate pathway that allows aromatic amino acid biosynthesis in plants and microorganisms. Its utilization in broad-spectrum herbicides, such as RoundUp®, has continued to increase since 1974; glyphosate, as well as its primary metabolite aminomethylphosphonic acid, is measured in soils, water, plants, animals and food. In humans, glyphosate is detected in blood and urine, especially in exposed workers, and is excreted within a few days. It has long been regarded as harmless in animals, but growing literature has reported health risks associated with glyphosate and glyphosate-based herbicides. In 2017, the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic" in humans. However, other national agencies did not tighten their glyphosate restrictions and even prolonged authorizations of its use. There are also discrepancies between countries' authorized levels, demonstrating an absence of a clear consensus on glyphosate to date. This review details the effects of glyphosate and glyphosate-based herbicides on fish and mammal health, focusing on the immune system. Increasing evidence shows that glyphosate and glyphosate-based herbicides exhibit cytotoxic and genotoxic effects, increase oxidative stress, disrupt the estrogen pathway, impair some cerebral functions, and allegedly correlate with some cancers. Glyphosate effects on the immune system appear to alter the complement cascade, phagocytic function, and lymphocyte responses, and increase the production of pro-inflammatory cytokines in fish. In mammals, including humans, glyphosate mainly has cytotoxic and genotoxic effects, causes inflammation, and affects lymphocyte functions and the interactions between microorganisms and the immune system. Importantly, even as many outcomes are still being debated, evidence points to a need for more studies to better decipher the risks from glyphosate and better regulation of its global utilization.
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Affiliation(s)
- Cindy Peillex
- Master de Biologie, École Normale Supérieure de Lyon, Université Claude Bernard Lyon I, Université de Lyon, Lyon, France
- Infectious and Immune Disease Axis, CHU de Québec-Université Laval Research Center, Quebec City, Canada
- ARThrite Research Center, Laval University, Quebec City, Canada
| | - Martin Pelletier
- Infectious and Immune Disease Axis, CHU de Québec-Université Laval Research Center, Quebec City, Canada
- ARThrite Research Center, Laval University, Quebec City, Canada
- Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Laval University, Quebec City, Canada
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Larsen K, Black P, Rydz E, Nicol AM, Peters CE. Using geographic information systems to estimate potential pesticide exposure at the population level in Canada. ENVIRONMENTAL RESEARCH 2020; 191:110100. [PMID: 32853660 DOI: 10.1016/j.envres.2020.110100] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 08/11/2020] [Accepted: 08/12/2020] [Indexed: 06/11/2023]
Abstract
Residents in close proximity to agricultural land are at risk of higher pesticide exposures. The purpose of this study was to generate national population-level exposure estimates for Canada for three commonly applied pesticides that are suspected carcinogens (2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate and chlorothalonil). Using geographic information systems, pesticide exposure was estimated for every - census subdivision (CSD) in Canada (n = 5054) by combining raster-based surfaces for the distribution of crops with average crop-specific pesticide application rates data. Analyses examined all identified crops in combination with different pesticide application rates to obtain a cumulative potential total exposure. Specifically, the number of acres of particular crops were calculated for each CSD and then multiplied by the average pesticide application rates data, summed across crops, and combined with population data by CSD to provide a potential pesticide exposure estimate for each CSD. Results demonstrate that the population exposure varies greatly depending on agricultural production by CSD region. For example, in Ontario, the 2,4-D application rate was an average of 361 kg/km2, while in Saskatchewan, which primarily grows field/cereal crops, 2,4-D application rates were much higher (3810 kg/km2). The highest potential exposures to all three pesticides were in the prairie provinces (Alberta, Saskatchewan, Manitoba) along with Prince Edward Island, Southern Quebec and British Columbia. This work can be used in conjunction with other exposure assessment approaches to better understand overall pesticide exposure among Canada's general population.
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Affiliation(s)
- Kristian Larsen
- CAREX Canada, Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada; Department of Geography and Planning, University of Toronto, Toronto, ON, Canada; Department of Geography and Environmental Studies, Ryerson University, Toronto, ON, Canada.
| | - Paleah Black
- CAREX Canada, Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada; Ecotox Consulting, Victoria, BC, Canada
| | - Ela Rydz
- CAREX Canada, Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada; Occupational Cancer Research Centre, Cancer Care Ontario, Toronto, ON, Canada
| | - Anne-Marie Nicol
- CAREX Canada, Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada; Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada
| | - Cheryl E Peters
- CAREX Canada, Faculty of Health Sciences, Simon Fraser University, Vancouver, BC, Canada; Preventive Oncology & Community Health Sciences. University of Calgary, Calgary, AB, Canada; Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, AB, Canada
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Shrestha S, Parks CG, Umbach DM, Richards-Barber M, Hofmann JN, Chen H, Blair A, Beane Freeman LE, Sandler DP. Pesticide use and incident Parkinson's disease in a cohort of farmers and their spouses. ENVIRONMENTAL RESEARCH 2020; 191:110186. [PMID: 32919961 PMCID: PMC7822498 DOI: 10.1016/j.envres.2020.110186] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 08/27/2020] [Accepted: 08/28/2020] [Indexed: 05/28/2023]
Abstract
BACKGROUND Extensive literature suggests an association between general pesticide use and Parkinson's disease (PD). However, with few exceptions, little is known about associations between specific pesticides and PD. OBJECTIVE We evaluated use of pesticides and incident PD in 38,274 pesticide applicators and 27,836 of their spouses in the Agricultural Health Study cohort followed over 20 years. METHODS We used self-reported information on ever-use of 50 specific pesticides as of enrollment for both applicators and spouses, and considered intensity-weighted lifetime days (IWLD) reported at enrollment and through the first 5-year follow-up among applicators. We estimated covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. We also examined heterogeneity in associations by history of head injury and chemical resistant glove use. RESULTS A total of 373 applicators and 118 spouses self-reported incident doctor-diagnosed PD. Ever-use of the insecticide terbufos (HR:1.31, 95%CI:1.02-1.68) and the herbicides trifluralin (HR:1.29, 95%CI: 0.99-1.70) and 2,4,5-T (HR:1.57, 95%CI:1.21-2.04) was associated with elevated PD risk. On the other hand, diazinon (HR:0.73, 95%CI: 0.58-0.94) and 2,4,5-TP (HR:0.39, 95%CI:0.25-0.62) were associated with reduced risk. We observed heterogeneity in ever-use associations by head injury and chemical-resistant glove use for some pesticides, with higher risk among those who reported a history of head injury, or who did not use gloves. PD risk was also elevated for applicators in the highest category of IWLD for dichlorvos, permethrin (animal use), and benomyl. CONCLUSIONS We found evidence of increased PD risk for some pesticides. Our results also suggest higher susceptibility for pesticide-associated PD among individuals with head injury as well as protection with use of chemical resistant gloves, although further research is needed to understand the impact of head injury. Research on current and newer pesticides, including mechanisms relevant to PD, is important given widespread pesticide use.
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Affiliation(s)
- Srishti Shrestha
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - Christine G Parks
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | - David M Umbach
- Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
| | | | - Jonathan N Hofmann
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Honglei Chen
- Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, MI, USA
| | - Aaron Blair
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Laura E Beane Freeman
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Dale P Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
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Choi J, Moon SI, Roh S. Assessment of relationship between farmer's syndrome and neurotoxic symptoms in farming couples. Environ Anal Health Toxicol 2020; 35:e2020015. [PMID: 33172227 PMCID: PMC7656165 DOI: 10.5620/eaht.2020015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 08/27/2020] [Indexed: 11/29/2022] Open
Abstract
The purpose of this study was to evaluate the relationship between farmer’s syndrome and neurotoxic symptoms in farming couples. The study was conducted on 348 farmers (174 couples) in Chungnam Province of South Korea. We obtained information on general and agricultural characteristics, farmer’s syndrome, and neurotoxic symptoms through face-to-face surveys from 2014 to 2019. The Korean version of the diagnostic standard scale was used for farmer’s syndrome, and the Swedish Q16 questionnaire was used for neurotoxic symptoms. Logistic regression analysis was used to identify neurotoxic symptoms affected by farmer’s syndrome. The prevalence of ‘positive’ neurotoxic symptoms was higher in wives (72.4%) than in husbands (56.9%). Compared with husbands with ‘negative and probable’ farmer’s syndrome (reference), husbands with ‘positive’ farmer’s syndrome were more likely to have ‘positive’ neurotoxic symptoms (odds ratio [OR] = 5.37, 95% confidence interval [CI] = 2.01–14.30). Compared with wives with ‘negative and probable’ farmer’s syndrome (reference), wives with ‘positive’ farmer’s syndrome were more likely to have ‘positive’ neurotoxic symptoms (OR = 7.07, 95% CI = 2.58–19.38). Therefore, neurotoxic symptoms in both husbands and wives were significantly associated with farmer’s syndrome. However, wives had a higher risk of neurotoxic symptoms than husbands. The findings of this study might be useful as important data for establishing and training agricultural safety and health policy.
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Affiliation(s)
- Jihee Choi
- Center for Farmers' Safety and Health, Dankook University Hospital, Cheonan, Republic of Korea
| | - Sun-In Moon
- Center for Farmers' Safety and Health, Dankook University Hospital, Cheonan, Republic of Korea
| | - Sangchul Roh
- Center for Farmers' Safety and Health, Dankook University Hospital, Cheonan, Republic of Korea.,Department of Occupational and Environment Medicine, College of Medicine, Dankook University, Cheonan, Republic of Korea
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He L, Hu W, Wang X, Liu Y, Jiang Y, Meng Y, Xiao Q, Guo X, Zhou Y, Bi Y, Lu Y. Analysis of Heavy Metal Contamination of Agricultural Soils and Related Effect on Population Health-A Case Study for East River Basin in China. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E1996. [PMID: 32197470 PMCID: PMC7143142 DOI: 10.3390/ijerph17061996] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 03/15/2020] [Accepted: 03/16/2020] [Indexed: 12/20/2022]
Abstract
To understand the heavy metal pollution in agricultural soils along the East River basin and assess the pollution related health effect to local residents, interviews and archived data were obtained to identify the study sites affected by polluted tailing. Soil samples were collected and tested for heavy metal content and the Comprehensive Pollution Index (CPI). The degree of pollution of agricultural soils in the area was assessed using GIS-based Spatial distribution map of heavy metals and the trend of soil heavy metal risk. Two villages (Matian and Zhudui) near the East River were included in this study for health effect assessment. A total of 193 residents aged 15 or above from each village were tested for the present status of chronic diseases. Convenient sampling method was used to collect blood samples from 78 residents for heavy metal concentration. The contents of Pb, Cd, As, Zn, and Cu in the agricultural soils were all over the standards with a moderate to severe CPI. Among these metals, Cd was the highest followed by Pb, and Cu was the lowest. The contents of Pb, Cd, As, and Zn tend to be higher in soils closer to the river. The prevalence of chronic diseases was over 30%, which is significantly higher than the report from the national central region (23.15%). The average blood lead level (BLL) among children under 14 years is 7.42 μg/dL. Although the adults in Matian village had a significantly higher BLL (χ2 = 8.70, p = 0.03) as compared to Zhudui village, there was no significant difference for the prevalence of chronic diseases between the two villages (χ2 = 3.23, p = 0.09). The mean BLL of children and the proportion of children with BLL ≥ 10 µg/dL in this study are equivalent to the national average. The higher BLL concentration and prevalence of chronic diseases in adults might be due to their long-term exposure to heavy metal contamination environment and higher background level of heavy metals. Findings from this study will form the baseline information for local government to the development of effective approaches to control the heavy metal contamination and reduce the pollution related adverse health effect on local residents.
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Affiliation(s)
- Liping He
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Wei Hu
- Department of Epidemiology and Health Statistics, Guangdong Medical University, Dongguan 523808, China;
| | - Xiaofeng Wang
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Yu Liu
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Yan Jiang
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Yanbin Meng
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Qipeng Xiao
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Xinxin Guo
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Yanfeng Zhou
- School of Public Health, Xiangnan University, Chenzhou 423000, China; (X.W.); (Y.L.); (Y.J.); (Y.M.); (Q.X.); (X.G.); (Y.Z.)
| | - Yongyi Bi
- School of Public Health, Wuhan University, Wuhan 430072, China;
| | - Yuanan Lu
- Department of Public Health Sciences, University of Hawaii at Mānoa, 1960 East-West Road, Honolulu, HI 96822, USA
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50
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Agostini LP, Dettogni RS, Dos Reis RS, Stur E, Dos Santos EVW, Ventorim DP, Garcia FM, Cardoso RC, Graceli JB, Louro ID. Effects of glyphosate exposure on human health: Insights from epidemiological and in vitro studies. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 705:135808. [PMID: 31972943 DOI: 10.1016/j.scitotenv.2019.135808] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 11/18/2019] [Accepted: 11/26/2019] [Indexed: 05/27/2023]
Abstract
Glyphosate (GLY) is a broad-spectrum, post-emergent, non-selective and synthetic universal herbicide, whose commercial formulations are referred to as glyphosate-based-herbicides (GBHs). These chemicals and their metabolites can be found in soil, air, water, as well as groundwater and food products. This review summarizes to summarize current in vitro and epidemiological studies investigating the effects of GLY exposure on human health. Recent human cell studies have reported several GLY and GBH toxicological effects and have contributed to a better understanding of the deleterious consequences associated with their exposure. However, these detrimental effects are dependent on the cell type, chemical composition, as well as magnitude and time of exposure, among other factors. Moreover, the deleterious effects of GLY exposure on human health were observed in epidemiological studies; however, most of these studies have not determined the GLY dosage to confirm a direct effect. While GLY toxicity is clear in human cells, epidemiological studies investigating individuals exposed to different levels of GLY have reported contradictory data. Therefore, based on currently available in vitro and epidemiological data, it is not possible to confirm the complete safety of GLY use, which will require additional comprehensive studies in animal models and humans.
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Affiliation(s)
- Lidiane P Agostini
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
| | - Raquel S Dettogni
- Endocrinology and Cell Toxicology Laboratory, Department of Morphology, Federal University of Espirito Santo, Vitoria, Brazil.
| | - Raquel S Dos Reis
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
| | - Elaine Stur
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
| | - Eldamária V W Dos Santos
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
| | - Diego P Ventorim
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
| | - Fernanda M Garcia
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
| | - Rodolfo C Cardoso
- Laboratory of Reproductive Neuroendocrinology, Department of Animal Science, Texas A&M University, United States of America
| | - Jones B Graceli
- Endocrinology and Cell Toxicology Laboratory, Department of Morphology, Federal University of Espirito Santo, Vitoria, Brazil
| | - Iúri D Louro
- Human and Molecular Genetics Center, Department of Biological Sciences, Federal University of Espirito Santo, Vitoria, Brazil
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