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Xiao Y, Rong D, Ye H, Duan Y, Qiao L, Zuo L, Liu L, Bayram H, Wang J. Music Aggravates Catechol-Induced Behavioural Abnormality and Redox Imbalance in Zebrafish. Int J Dev Neurosci 2025; 85:e70018. [PMID: 40271718 DOI: 10.1002/jdn.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/08/2025] [Accepted: 04/12/2025] [Indexed: 04/25/2025] Open
Abstract
Catechol, also known as pyrocatechol, is a widespread antioxidant carcinogen that has been shown to cause central nervous system damage and metabolic abnormalities, and in zebrafish, it has been shown that exposure to aqueous solutions of catechol results in reduced pigmentation and decreased basal locomotor rate in juvenile zebrafish. However, the effects of catechol on zebrafish redox and behaviour are unknown. The aim of this study was to investigate the effects of catechol on oxidative stress levels in early zebrafish development and on behaviour in later stages of zebrafish development and to attempt to intervene in this effect with music therapy. We exposed zebrafish adults and juveniles to catechol separately, tested zebrafish juveniles for various redox indices and found that zebrafish juveniles had increased levels of reactive oxygen species and decreased total antioxidant capacity and lipid peroxidation capacity, and we tested zebrafish adults for behavioural studies and found that anxiety behaviours increased as social cohesion decreased. We then conducted a music therapy intervention for catechol exposure in adult zebrafish and found that music therapy exacerbated catechol-induced behavioural abnormalities and altered oxidative levels, whether zebrafish were exposed to both catechol and classical music or whether the catechol exposure was followed by a 12-day classical music intervention after 12 days of catechol exposure. In summary, this study revealed for the first time that catechol caused redox imbalance in juvenile zebrafish and socially disturbed, anxious behaviour in adults and found that music treatment worsened this behavioural abnormality. This study provides new insights into the effects of catechol on zebrafish and suggests that the therapeutic effects of music therapy may have a double-edged effect.
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Affiliation(s)
- Yaqian Xiao
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Dechang Rong
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Hongjia Ye
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Yifan Duan
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Lichen Qiao
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Lanlan Zuo
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Lingtong Liu
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
| | - Hasan Bayram
- Department of Pulmonary Medicine, School of Medicine, Koc University, Istanbul, Turkey
| | - Jun Wang
- National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China
- International Center for Redox Biology & Precision Medicine of Hubei Province, Hubei University of Technology, Wuhan, Hubei Province, China
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Flores-Prieto B, Manzo-Denes J, Hernández-Aguilar ME, Coria-Avila GA, Herrera-Covarrubias D, Aranda-Abreu GE, Rojas-Durán F, Pérez-Estudillo CA, Suárez-Medellín J, Toledo-Cárdenas MR. Effects of Valproic Acid Embryonic Exposure on Zebrafish: A Systematic Review and Meta-Analysis. NEUROSCI 2024; 5:650-665. [PMID: 39728678 DOI: 10.3390/neurosci5040046] [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: 11/05/2024] [Accepted: 11/22/2024] [Indexed: 12/28/2024] Open
Abstract
Exposure to valproic acid (VPA) during embryogenesis has become a valuable tool for modeling neurodevelopmental disorders in animal models such as zebrafish (Danio rerio). This article examines the effects of embryonic exposure to VPA in zebrafish on the basis of 39 articles sourced from PubMed and Google Scholar. We conducted a systematic review and meta-analysis to elucidate the common impacts of VPA exposure and reported that VPA significantly altered development at various levels. Behaviorally, zebrafish exposed to VPA exhibit notable changes in their social interaction patterns. Physiologically, VPA exposure leads to significant alterations, including decreased heart rates, increased mortality rates, and pronounced morphological abnormalities. Pharmacological exposure has been linked to neuroanatomical and neurochemical changes. At the genetic level, VPA exposure is associated with the differential expression of genes involved in neurodevelopment and neuronal function. The synthesized data from these studies underscore the utility of zebrafish as a model organism for investigating the effects of teratogen exposure on neurodevelopment.
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Affiliation(s)
| | - Jorge Manzo-Denes
- Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91070, Mexico
| | | | | | | | | | - Fausto Rojas-Durán
- Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91070, Mexico
| | | | - Jorge Suárez-Medellín
- Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa 91070, Mexico
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Al-Beltagi M, Saeed NK, Bediwy AS, Bediwy EA, Elbeltagi R. Decoding the genetic landscape of autism: A comprehensive review. World J Clin Pediatr 2024; 13:98468. [PMID: 39350903 PMCID: PMC11438927 DOI: 10.5409/wjcp.v13.i3.98468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/29/2024] [Accepted: 08/01/2024] [Indexed: 08/30/2024] Open
Abstract
BACKGROUND Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings. Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD, influencing both diagnosis and therapeutic strategies. AIM To explore the genetic architecture of ASD, elucidate mechanistic insights into genetic mutations, and examine gene-environment interactions. METHODS A comprehensive systematic review was conducted, integrating findings from studies on genetic variations, epigenetic mechanisms (such as DNA methylation and histone modifications), and emerging technologies [including Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 and single-cell RNA sequencing]. Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar. RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD, yet many cases remain unexplained by known factors, suggesting undiscovered genetic components. Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving. Epigenetic modifications, particularly DNA methylation and non-coding RNAs, also play significant roles in ASD pathogenesis. Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data. CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments. Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice. Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies, ultimately enhancing outcomes for individuals affected by ASD.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Alghrabia, Tanta 31511, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Muharraq, Busaiteen 15503, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Alghrabia, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Eman A Bediwy
- Internal Medicine, Faculty of Medicine, Tanta University, Algharbia, Tanta 31527, Egypt
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland-Bahrain, Muharraq, Busiateen 15503, Bahrain
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Borba JV, Canzian J, Resmim CM, Silva RM, Duarte MCF, Mohammed KA, Schoenau W, Adedara IA, Rosemberg DB. Towards zebrafish models to unravel translational insights of obsessive-compulsive disorder: A neurobehavioral perspective. Neurosci Biobehav Rev 2024; 162:105715. [PMID: 38734195 DOI: 10.1016/j.neubiorev.2024.105715] [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: 01/30/2024] [Revised: 04/08/2024] [Accepted: 05/04/2024] [Indexed: 05/13/2024]
Abstract
Obsessive-compulsive disorder (OCD) is a chronic and debilitating illness that has been considered a polygenic and multifactorial disorder, challenging effective therapeutic interventions. Although invaluable advances have been obtained from human and rodent studies, several molecular and mechanistic aspects of OCD etiology are still obscure. Thus, the use of non-traditional animal models may foster innovative approaches in this field, aiming to elucidate the underlying mechanisms of disease from an evolutionary perspective. The zebrafish (Danio rerio) has been increasingly considered a powerful organism in translational neuroscience research, especially due to the intrinsic features of the species. Here, we outline target mechanisms of OCD for translational research, and discuss how zebrafish-based models can contribute to explore neurobehavioral aspects resembling those found in OCD. We also identify possible advantages and limitations of potential zebrafish-based models, as well as highlight future directions in both etiological and therapeutic research. Lastly, we reinforce the use of zebrafish as a promising tool to unravel the biological basis of OCD, as well as novel pharmacological therapies in the field.
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Affiliation(s)
- João V Borba
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil.
| | - Julia Canzian
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil
| | - Cássio M Resmim
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil
| | - Rossano M Silva
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil
| | - Maria C F Duarte
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil
| | - Khadija A Mohammed
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil
| | - William Schoenau
- Department of Physiology and Pharmacology, Health Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil
| | - Isaac A Adedara
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Denis B Rosemberg
- Laboratory of Experimental Neuropsychobiology, Department of Biochemistry and Molecular Biology, Natural and Exact Sciences Center, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; Graduate Program in Biological Sciences: Toxicological Biochemistry, Federal University of Santa Maria, 1000 Roraima Avenue, Santa Maria, RS 97105-900, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), 309 Palmer Court, Slidell, LA 70458, USA.
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Merola C, Caioni G, Bertolucci C, Lucon-Xiccato T, Savaşçı BB, Tait S, Casella M, Camerini S, Benedetti E, Perugini M. Embryonic and larval exposure to propylparaben induces developmental and long-term neurotoxicity in zebrafish model. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 912:168925. [PMID: 38040379 DOI: 10.1016/j.scitotenv.2023.168925] [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: 08/08/2023] [Revised: 11/23/2023] [Accepted: 11/25/2023] [Indexed: 12/03/2023]
Abstract
Parabens are preservatives found in cosmetics, processed foods, and medications. The harmful repercussions on the central nervous system by one of the most common parabens, propylparaben (PrP), are yet unknown, especially during development. In this study, the neurodevelopmental effects of PrP and long-term neurotoxicity were investigated in the zebrafish model, using an integrated approach. Zebrafish embryos were exposed to two different concentrations of PrP (10 and 1000 μg/L), then larvae were examined for their behavioral phenotypes (open-field behavior, startle response, and circadian rhythmicity) and relevant brain markers (cyp19a1b, pax6a, shank3a, and gad1b). Long-term behavioral and cognitive impacts on sociability, cerebral functional asymmetry and thigmotaxis were also examined on juveniles at 30 dpf and 60 dpf. Moreover, proteomics and gene expression analysis were assessed in brains of 60 dpf zebrafish. Interestingly, thigmotaxis was decreased by the high dose in larvae and increased by the low dose in juveniles. The expression of shank3a and gad1b genes was repressed by both PrP concentrations pointing to possible effects of PrP on neurodevelopment and synaptogenesis. Proteomics analysis evidenced alterations related to brain development and lipid metabolism. Overall, the results demonstrated that early-life exposure to PrP promotes developmental and persistent neurobehavioral alterations in the zebrafish model, affecting genes and protein levels possibly associated with brain diseases.
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Affiliation(s)
- Carmine Merola
- Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Teramo, Italy.
| | - Giulia Caioni
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Cristiano Bertolucci
- Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
| | - Tyrone Lucon-Xiccato
- Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
| | - Beste Başak Savaşçı
- Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy; Unit of Evolutionary Biology/Systematic Zoology, Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
| | - Sabrina Tait
- Gender-specific prevention and health Unit, Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Rome, Italy.
| | - Marialuisa Casella
- Mass Spectrometry Unit, Core Facilities, Istituto Superiore di Sanità, Rome, Italy.
| | - Serena Camerini
- Mass Spectrometry Unit, Core Facilities, Istituto Superiore di Sanità, Rome, Italy.
| | - Elisabetta Benedetti
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
| | - Monia Perugini
- Department of Bioscience and Agro-Food and Environmental Technology, University of Teramo, Teramo, Italy.
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Deng J, Liu C, Hu M, Hu C, Lin J, Li Q, Xu X. Dynamic Regulation of brsk2 in the Social and Motor Development of Zebrafish: A Developmental Behavior Analysis. Int J Mol Sci 2023; 24:16506. [PMID: 38003696 PMCID: PMC10671324 DOI: 10.3390/ijms242216506] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/26/2023] [Accepted: 11/11/2023] [Indexed: 11/26/2023] Open
Abstract
Both social and motor development play an essential role in an individual's physical, psychological, and social well-being. It is essential to conduct a dynamic analysis at multiple time points during the developmental process as it helps us better understand and evaluate the trajectory and changes in individual development. Recently, some studies found that mutations in the BRSK2 gene may contribute to motor impairments, delays in achieving motor milestones, and deficits in social behavior and communication skills in patients. However, little is known about the dynamic analysis of social and motor development at multiple time points during the development of the brsk2 gene. We generated a novel brsk2-deficient (brsk2ab-/-) zebrafish model through CRISPR/Cas9 editing and conducted comprehensive morphological and neurobehavioral evaluations, including that of locomotor behaviors, social behaviors, and anxiety behaviors from the larval to adult stages of development. Compared to wild-type zebrafish, brsk2ab-/- zebrafish exhibited a catch-up growth pattern of body length and gradually improved locomotor activities during the developmental process. In contrast, multimodal behavior tests showed that the brsk2ab-/- zebrafish displayed escalating social deficiency and anxiety-like behaviors over time. We reported for the first time that the brsk2 gene had dynamic regulatory effects on motor and social development. It helps us understand developmental trends, capture changes, facilitate early interventions, and provide personalized support and development opportunities for individuals.
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Affiliation(s)
- Jingxin Deng
- Division of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.D.); (M.H.); (C.H.)
| | - Chunxue Liu
- Division of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.D.); (M.H.); (C.H.)
| | - Meixin Hu
- Division of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.D.); (M.H.); (C.H.)
| | - Chunchun Hu
- Division of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.D.); (M.H.); (C.H.)
| | - Jia Lin
- Center for Translational Medicine, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.L.); (Q.L.)
| | - Qiang Li
- Center for Translational Medicine, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.L.); (Q.L.)
| | - Xiu Xu
- Division of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, 399 Wanyuan Road, Shanghai 201102, China; (J.D.); (M.H.); (C.H.)
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Abu Bakar N, Wan Ibrahim WN, Zulkiflli AR, Saleh Hodin NA, Kim TY, Ling YS, Md Ajat MM, Shaari K, Shohaimi S, Nasruddin NS, Mohd Faudzi SM, Kim CH. Embryonic mercury exposure in zebrafish: Alteration of metabolites and gene expression, related to visual and behavioral impairments. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 256:114862. [PMID: 37004432 DOI: 10.1016/j.ecoenv.2023.114862] [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: 01/03/2023] [Revised: 03/05/2023] [Accepted: 03/30/2023] [Indexed: 06/19/2023]
Abstract
The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl2), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl2 from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl2 toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish.
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Affiliation(s)
- Noraini Abu Bakar
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Wan Norhamidah Wan Ibrahim
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Abdul Rahman Zulkiflli
- Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Nur Atikah Saleh Hodin
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Tae-Yoon Kim
- Department of Biology, Chungnam National University, Daejeon 34134, Republic of Korea
| | - Yee Soon Ling
- Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400 Kota Kinabalu, Sabah, Malaysia
| | - Mohd Mokrish Md Ajat
- Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400, Malaysia
| | - Khozirah Shaari
- Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Shamarina Shohaimi
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Nurrul Shaqinah Nasruddin
- Centre for Craniofacial Diagnostics, Faculty of Dentistry, Universiti Kebangsaan Malaysia (UKM), 50300 Kuala Lumpur, Malaysia
| | - Siti Munirah Mohd Faudzi
- Natural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
| | - Cheol-Hee Kim
- Department of Biology, Chungnam National University, Daejeon 34134, Republic of Korea.
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Chen YS, Zhang SM, Tan W, Zhu Q, Yue CX, Xiang P, Li JQ, Wei Z, Zeng Y. Early 7,8-Dihydroxyflavone Administration Ameliorates Synaptic and Behavioral Deficits in the Young FXS Animal Model by Acting on BDNF-TrkB Pathway. Mol Neurobiol 2023; 60:2539-2552. [PMID: 36680734 DOI: 10.1007/s12035-023-03226-w] [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: 09/21/2022] [Accepted: 12/30/2022] [Indexed: 01/22/2023]
Abstract
Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and the most common cause of autism spectrum disorders. FXS patients exhibit severe syndromic features and behavioral alterations, including anxiety, hyperactivity, impulsivity, and aggression, in addition to cognitive impairment and seizures. At present, there are no effective treatments or cures for FXS. Previously, we have found the divergence of BDNF-TrkB signaling trajectories is associated with spine defects in early postnatal developmental stages of Fmr1 KO mice. Here, young fragile X mice were intraperitoneal injection with 7,8-Dihydroxyflavone (7,8-DHF), a high affinity tropomyosin receptor kinase B (TrkB) agonist. 7,8-DHF ameliorated morphological abnormities in dendritic spine and synaptic structure and rescued synaptic and hippocampus-dependent cognitive dysfunction. These observed improvements of 7,8-DHF involved decreased protein levels of BDNF, p-TrkBY816, p-PLCγ, and p-CaMKII in the hippocampus. In addition, 7,8-DHF intervention in primary hippocampal neurons increased p-TrkBY816 and activated the PLCγ1-CaMKII signaling pathway, leading to improvement of neuronal morphology. This study is the first to account for early life synaptic impairments, neuronal morphological, and cognitive delays in FXS in response to the abnormal BDNF-TrkB pathway. Present studies provide novel evidences about the effective early intervention in FXS mice at developmental stages and a strategy to produce powerful impacts on neural development, synaptic plasticity, and behaviors.
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Affiliation(s)
- Yu-Shan Chen
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Si-Ming Zhang
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Wei Tan
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Qiong Zhu
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Chao-Xiong Yue
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Peng Xiang
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Jin-Quan Li
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Zhen Wei
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China
| | - Yan Zeng
- Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, 430065, China.
- Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, China.
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9
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Abu Bakar N, Wan Ibrahim WN, Che Abdullah CA, Ramlan NF, Shaari K, Shohaimi S, Mediani A, Nasruddin NS, Kim CH, Mohd Faudzi SM. Embryonic Arsenic Exposure Triggers Long-Term Behavioral Impairment with Metabolite Alterations in Zebrafish. TOXICS 2022; 10:493. [PMID: 36136458 PMCID: PMC9502072 DOI: 10.3390/toxics10090493] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/19/2022] [Accepted: 08/21/2022] [Indexed: 05/10/2023]
Abstract
Arsenic trioxide (As2O3) is a ubiquitous heavy metal in the environment. Exposure to this toxin at low concentrations is unremarkable in developing organisms. Nevertheless, understanding the underlying mechanism of its long-term adverse effects remains a challenge. In this study, embryos were initially exposed to As2O3 from gastrulation to hatching under semi-static conditions. Results showed dose-dependent increased mortality, with exposure to 30-40 µM As2O3 significantly reducing tail-coiling and heart rate at early larval stages. Surviving larvae after 30 µM As2O3 exposure showed deficits in motor behavior without impairment of anxiety-like responses at 6 dpf and a slight impairment in color preference behavior at 11 dpf, which was later evident in adulthood. As2O3 also altered locomotor function, with a loss of directional and color preference in adult zebrafish, which correlated with changes in transcriptional regulation of adsl, shank3a, and tsc1b genes. During these processes, As2O3 mainly induced metabolic changes in lipids, particularly arachidonic acid, docosahexaenoic acid, prostaglandin, and sphinganine-1-phosphate in the post-hatching period of zebrafish. Overall, this study provides new insight into the potential mechanism of arsenic toxicity leading to long-term learning impairment in zebrafish and may benefit future risk assessments of other environmental toxins of concern.
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Affiliation(s)
- Noraini Abu Bakar
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Wan Norhamidah Wan Ibrahim
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Che Azurahanim Che Abdullah
- Department of Physics, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia
- The Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Nurul Farhana Ramlan
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Khozirah Shaari
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Shamarina Shohaimi
- Department of Biology, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia
| | - Ahmed Mediani
- Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia
| | - Nurrul Shaqinah Nasruddin
- Centre for Craniofacial Diagnostics, Faculty of Dentistry, Universiti Kebangsaan Malaysia (UKM), Kuala Lumpur 50300, Malaysia
| | - Cheol-Hee Kim
- Department of Biology, Chungnam National University, Daejeon 34134, Korea
| | - Siti Munirah Mohd Faudzi
- Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Malaysia
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10
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Neklyudova A, Smirnov K, Rebreikina A, Martynova O, Sysoeva O. Electrophysiological and Behavioral Evidence for Hyper- and Hyposensitivity in Rare Genetic Syndromes Associated with Autism. Genes (Basel) 2022; 13:671. [PMID: 35456477 PMCID: PMC9027402 DOI: 10.3390/genes13040671] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/29/2022] [Accepted: 04/05/2022] [Indexed: 01/27/2023] Open
Abstract
Our study reviewed abnormalities in spontaneous, as well as event-related, brain activity in syndromes with a known genetic underpinning that are associated with autistic symptomatology. Based on behavioral and neurophysiological evidence, we tentatively subdivided the syndromes on primarily hyper-sensitive (Fragile X, Angelman) and hypo-sensitive (Phelan-McDermid, Rett, Tuberous Sclerosis, Neurofibromatosis 1), pointing to the way of segregation of heterogeneous idiopathic ASD, that includes both hyper-sensitive and hypo-sensitive individuals. This segmentation links abnormalities in different genes, such as FMR1, UBE3A, GABRB3, GABRA5, GABRG3, SHANK3, MECP2, TSC1, TSC2, and NF1, that are causative to the above-mentioned syndromes and associated with synaptic transmission and cell growth, as well as with translational and transcriptional regulation and with sensory sensitivity. Excitation/inhibition imbalance related to GABAergic signaling, and the interplay of tonic and phasic inhibition in different brain regions might underlie this relationship. However, more research is needed. As most genetic syndromes are very rare, future investigations in this field will benefit from multi-site collaboration with a common protocol for electrophysiological and event-related potential (EEG/ERP) research that should include an investigation into all modalities and stages of sensory processing, as well as potential biomarkers of GABAergic signaling (such as 40-Hz ASSR).
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Affiliation(s)
- Anastasia Neklyudova
- Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, 117485 Moscow, Russia; (A.N.); (K.S.); (A.R.); (O.M.)
| | - Kirill Smirnov
- Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, 117485 Moscow, Russia; (A.N.); (K.S.); (A.R.); (O.M.)
| | - Anna Rebreikina
- Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, 117485 Moscow, Russia; (A.N.); (K.S.); (A.R.); (O.M.)
- Sirius Center for Cognitive Research, Sirius University of Science and Technology, 354340 Sochi, Russia
| | - Olga Martynova
- Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, 117485 Moscow, Russia; (A.N.); (K.S.); (A.R.); (O.M.)
| | - Olga Sysoeva
- Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Science, 117485 Moscow, Russia; (A.N.); (K.S.); (A.R.); (O.M.)
- Sirius Center for Cognitive Research, Sirius University of Science and Technology, 354340 Sochi, Russia
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