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Liang B, Zhou Y, Jiang C, Zhao T, Qin D, Gao F. Role and related mechanisms of non-invasive brain stimulation in the treatment of Tourette syndrome. Brain Res Bull 2025; 222:111258. [PMID: 39954818 DOI: 10.1016/j.brainresbull.2025.111258] [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: 11/12/2024] [Revised: 02/03/2025] [Accepted: 02/10/2025] [Indexed: 02/17/2025]
Abstract
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by impaired or delayed functional development. Although the pathology of TS remains to be determined, the continuous development of science and technology has provided new perspectives to understand its pathological mechanism. Research into non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation and direct current stimulation, have shown promising therapeutic potential in clinical studies. Furthermore, NIBS has been shown to affect the brain of patients with TS, including synaptic transmission, release of neurotransmitters, in addition to the activation of microglial cells and astrocytes. However, an exploration of the innate mechanisms is still lacking. This review aims to summarize the pathogenesis of TS and intervention with NIBS in clinical patients with TS. It aims to provide a theoretical basis for more in-depth investigations of innovative therapies for TS in the future.
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Affiliation(s)
- Boshen Liang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China
| | - Yang Zhou
- The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China
| | - Chengting Jiang
- Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China
| | - Ting Zhao
- Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
| | - Dongdong Qin
- Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Neuropsychiatric Disease, Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China.
| | - Fabao Gao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Yunnan University of Chinese Medicine, Kunming, Yunnan 650500, China.
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Nayak U, Manikkath J, Arora D, Mudgal J. Impact of neuroinflammation on brain glutamate and dopamine signalling in schizophrenia: an update. Metab Brain Dis 2025; 40:119. [PMID: 39907868 PMCID: PMC11799129 DOI: 10.1007/s11011-025-01548-3] [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: 09/26/2024] [Accepted: 01/30/2025] [Indexed: 02/06/2025]
Abstract
Schizophrenia is one of the most severe and chronic psychiatric disorders. Over the years, numerous treatment options have been introduced for schizophrenia. Although they are relatively successful in managing the positive symptoms of schizophrenia, most of the current treatments have a negligible effect on the negative and cognitive symptoms. Thus, none of them could prevent the relapse of psychotic episodes. Among the numerous hypotheses explaining the development and progression of schizophrenia, the cytokine hypothesis explains the role of inflammatory markers as a significant culprit in the development of schizophrenia. Elevated cytokines are reported in animal models and schizophrenic patients. The cytokine hypothesis is based on how increased inflammatory markers can cause changes in the dopaminergic, glutamate, and tryptophan metabolism pathways, like that observed in schizophrenic patients. Reasons, such as autoimmune disease, maternal immune activation, infection, etc., can pave the way for the development of schizophrenia and are associated with the negative, positive and cognitive symptoms of schizophrenia. Thus, there is a need to focus on the significance of anti-inflammatory drugs against these symptoms. The development of new treatment strategies in the management of schizophrenia can provide better therapeutic outcomes in terms of the severity of symptoms and treatment of drug-resistant schizophrenia. This review attempts to explain the association between elevated inflammatory markers and various neurotransmitters, and the possible use of medications like nonsteroidal anti-inflammatory drugs, monoclonal antibodies, statins, and estrogens as adjuvant therapy. Over the years, these hypotheses have been the basis for drug discovery for the treatment of schizophrenia.
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Affiliation(s)
- Usha Nayak
- Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Jyothsna Manikkath
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Devinder Arora
- School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, 4222, Australia
| | - Jayesh Mudgal
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
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Chauveau F, Winkeler A, Chalon S, Boutin H, Becker G. PET imaging of neuroinflammation: any credible alternatives to TSPO yet? Mol Psychiatry 2025; 30:213-228. [PMID: 38997465 DOI: 10.1038/s41380-024-02656-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/14/2024]
Abstract
Over the last decades, the role of neuroinflammation in neuropsychiatric conditions has attracted an exponentially growing interest. A key driver for this trend was the ability to image brain inflammation in vivo using PET radioligands targeting the Translocator Protein 18 kDa (TSPO), which is known to be expressed in activated microglia and astrocytes upon inflammatory events as well as constitutively in endothelial cells. TSPO is a mitochondrial protein that is expressed mostly by microglial cells upon activation but is also expressed by astrocytes in some conditions and constitutively by endothelial cells. Therefore, our current understanding of neuroinflammation dynamics is hampered by the lack of alternative targets available for PET imaging. We performed a systematic search and review on radiotracers developed for neuroinflammation PET imaging apart from TSPO. The following targets of interest were identified through literature screening (including previous narrative reviews): P2Y12R, P2X7R, CSF1R, COX (microglial targets), MAO-B, I2BS (astrocytic targets), CB2R & S1PRs (not specific of a single cell type). We determined the level of development and provided a scoping review for each target. Strikingly, astrocytic biomarker MAO-B has progressed in clinical investigations the furthest, while few radiotracers (notably targeting S1P1Rs, CSF1R) are being implemented in clinical investigations. Other targets such as CB2R and P2X7R have proven disappointing in clinical studies (e.g. poor signal, lack of changes in disease conditions, etc.). While astrocytic targets are promising, development of new biomarkers and tracers specific for microglial activation has proven challenging.
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Affiliation(s)
- Fabien Chauveau
- Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, Inserm U1028, CNRS UMR5292, BIORAN, Groupement Hospitalier Est - CERMEP, 59 boulevard Pinel, 69677, Bron, Cedex, France
| | - Alexandra Winkeler
- Université Paris-Saclay, Inserm, CNRS, CEA, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du général Leclerc, 91401, Orsay, France
| | - Sylvie Chalon
- UMR 1253 iBrain, Université de Tours - INSERM, Bâtiment Planiol, UFR de Médecine, 10 Boulevard Tonnellé, 37032, Tours, Cedex 01, France
| | - Hervé Boutin
- UMR 1253 iBrain, Université de Tours - INSERM, Bâtiment Planiol, UFR de Médecine, 10 Boulevard Tonnellé, 37032, Tours, Cedex 01, France.
| | - Guillaume Becker
- Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, Inserm U1028, CNRS UMR5292, BIORAN, Groupement Hospitalier Est - CERMEP, 59 boulevard Pinel, 69677, Bron, Cedex, France
- Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail, 14 rue Pierre et Marie Curie, 94701, Maisons-Alfort, Cedex, France
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Shamakina IY, Anokhin PK, Ageldinov RA, Kokhan VS. Neuroimmune Characteristics of Animals with Prenatal Alcohol Intoxication. BIOCHEMISTRY. BIOKHIMIIA 2024; 89:1922-1929. [PMID: 39647821 DOI: 10.1134/s0006297924110063] [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: 05/28/2024] [Revised: 07/22/2024] [Accepted: 07/29/2024] [Indexed: 12/10/2024]
Abstract
Neuroinflammation can be an important factor of many disorders in central nervous system (CNS) including cognitive dysfunction, affective disorders, and addictive behavior associated with prenatal alcohol exposure and presented in early adulthood. In this study we used an experimental rodent model of prenatal alcohol (PA) exposure (consumption of a 10% ethanol solution by female Wistar rats throughout pregnancy), multiplex immunofluorescence analysis of interleukins (IL-1α, IL-1β, IL-3, IL-6, IL-9, and IL-12), tumor necrosis factor (TNF-α), and chemokine CCL5, as well as quantitative real-time PCR to assess the level of cytokine mRNAs in the prefrontal cortex of the sexually mature (PND60) offspring - male and female rats with prenatal alcohol intoxication and control animals. Significant decrease in the content of TNF-α and interleukins IL-1β, IL-3, IL-6, IL-9 was detected in the prefrontal cortex of male, but not in the female PA offspring. Importantly, PA males also showed decrease in the level of TNF-α mRNA in the prefrontal cortex by 45% compared to the control males, which may underlie the detected decrease in its content. Taken together, our study demonstrates that a number of neuroimmune factors are regulated in a sex-specific manner in the prefrontal cortex and are differentially affected in males and females by the prenatal exposure to alcohol. Sex factor must be taken into account when conducting further translational studies of the fetal alcohol spectrum disorders and developing new methods for prevention and therapy.
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Affiliation(s)
- Inna Yu Shamakina
- Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, 119002, Russia.
| | - Petr K Anokhin
- Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, 119002, Russia
- Artificial Intelligence Research Institute, Moscow, 121170, Russia
| | - Ruslan A Ageldinov
- Scientific Center for Biomedical Technologies of the Federal Medical and Biological Agency of Russia, Svetlye Gory, 143442, Russia
| | - Viktor S Kokhan
- Serbsky National Medical Research Center of Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, 119002, Russia
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Idowu OK, Dosumu OO, Boboye AS, Oremosu AA, Mohammed AA. Lauric acid with or without levodopa ameliorates Parkinsonism in genetically modified model of Drosophila melanogaster via the oxidative-inflammatory-apoptotic pathway. Brain Behav 2024; 14:e70001. [PMID: 39245995 PMCID: PMC11381577 DOI: 10.1002/brb3.70001] [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: 11/13/2023] [Revised: 06/10/2024] [Accepted: 07/08/2024] [Indexed: 09/10/2024] Open
Abstract
BACKGROUND Parkinson's disease (PD), the most prevalent type of Parkinsonism, is a progressive neurological condition characterized by a range of motor and non-motor symptoms. The complicated etiology of PD is thought to involve a summation of aging, genetic predisposition, and environmental variables. However, the α-synuclein protein plays a significant role in the disease's pathophysiology. MATERIALS AND METHODS The UAS-α-Syn and Ddc-Gal4 strains were crossed to produce offspring referred to as PD flies. The entire population of flies was divided into five groups, each having about 100 flies and five replicates. The control group (w1118) and the PD group not receiving treatment were exposed to lauric acid (LA)/levodopa (LD)-free diet, while the PD groups that received treatments were fed with either a 250 mg/kg LA diet, a 250 mg/kg LD diet, or a combination of the two for 21 days. Longevity, geotaxis, and olfactory assays were performed in addition to other biochemical tests. RESULTS As a result of the overexpression of α-synuclein, the locomotive capacity, lifespan, and antioxidant status were all significantly (p < .05) reduced, and the apoptotic and neuroinflammatory activities were increased. Nevertheless, the majority of the treated flies improved significantly (p < .05). CONCLUSION LA, whether combined with LD or not, elicited a significant response in α-synuclein/dopa decarboxylase genetically modified Drosophila melanogaster Parkinsonism models.
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Affiliation(s)
- Olumayowa K Idowu
- Department of Anatomy, College of Medicine, University of Lagos, Lagos, Nigeria
- Department of Anatomy, College of Health Sciences, Osun State University, Osogbo, Nigeria
| | - Olufunke O Dosumu
- Department of Anatomy, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Ayodeji S Boboye
- Department of Anatomy, College of Health Sciences, Federal University of Technology, Akure, Nigeria
| | - Ademola A Oremosu
- Department of Anatomy, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Abdullahi A Mohammed
- Department of Human Anatomy, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Butare, Rwanda
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Hawkes C, Dale RC, Scher S, Cornish JL, Perez DL, Santoro JD, Fernandes S, Kozlowska K. Bridging the Divide: An Integrated Neurobio-Psycho-Social Approach to Treating Antibody Negative Inflammatory Encephalitis in a School-Aged Child. Harv Rev Psychiatry 2024; 32:101-116. [PMID: 38728570 DOI: 10.1097/hrp.0000000000000395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/12/2024]
Affiliation(s)
- Clare Hawkes
- From Kids Neuroscience Centre (Dr. Dale), The Children's Hospital at Westmead (Drs. Dale, Hawkes, and Kozlowska), Westmead, AUS; Faculty of Medicine and Health, The Children's Hospital at Westmead Clinical School (Drs. Dale and Kozlowska), and Brain and Mind Centre (Dr. Dale), University of Sydney, Sydney, AUS; Harvard Medical School (Drs. Scher, Perez, and Fernandes); McLean Hospital, Belmont, MA (Drs. Scher and Fernandes); Specialty in Psychiatry, University of Sydney School of Medicine, Sydney, AUS (Drs. Scher and Kozlowska); School of Psychological Sciences and Centre for Emotional Health, Macquarie University (Dr. Cornish); Department of Neurology and Department of Psychiatry, Massachusetts General Hospital, Boston, MA (Dr. Perez); Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA (Dr. Santoro); Department of Neurology, Keck School of Medicine of the University of Southern California (Dr. Santoro); The Brain Dynamics Centre, The Westmead Institute for Medical Research, Westmead, AUS (Dr. Kozlowska)
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Mosquera FEC, Guevara-Montoya MC, Serna-Ramirez V, Liscano Y. Neuroinflammation and Schizophrenia: New Therapeutic Strategies through Psychobiotics, Nanotechnology, and Artificial Intelligence (AI). J Pers Med 2024; 14:391. [PMID: 38673018 PMCID: PMC11051547 DOI: 10.3390/jpm14040391] [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: 03/13/2024] [Revised: 03/29/2024] [Accepted: 04/03/2024] [Indexed: 04/28/2024] Open
Abstract
The prevalence of schizophrenia, affecting approximately 1% of the global population, underscores the urgency for innovative therapeutic strategies. Recent insights into the role of neuroinflammation, the gut-brain axis, and the microbiota in schizophrenia pathogenesis have paved the way for the exploration of psychobiotics as a novel treatment avenue. These interventions, targeting the gut microbiome, offer a promising approach to ameliorating psychiatric symptoms. Furthermore, advancements in artificial intelligence and nanotechnology are set to revolutionize psychobiotic development and application, promising to enhance their production, precision, and effectiveness. This interdisciplinary approach heralds a new era in schizophrenia management, potentially transforming patient outcomes and offering a beacon of hope for those afflicted by this complex disorder.
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Affiliation(s)
| | | | | | - Yamil Liscano
- Grupo de Investigación en Salud Integral (GISI), Departamento Facultad de Salud, Universidad Santiago de Cali, Cali 760035, Colombia; (F.E.C.M.); (M.C.G.-M.); (V.S.-R.)
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Wu Y, Wang Y, Hu A, Shu X, Huang W, Liu J, Wang B, Zhang R, Yue M, Yang C. Lactobacillus plantarum-derived postbiotics prevent Salmonella-induced neurological dysfunctions by modulating gut-brain axis in mice. Front Nutr 2022; 9:946096. [PMID: 35967771 PMCID: PMC9365972 DOI: 10.3389/fnut.2022.946096] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/20/2022] [Indexed: 01/04/2023] Open
Abstract
Postbiotics are the inactive bacteria and/or metabolites of beneficial microbes which have been recently found to be as effective as their live probiotic. This study aimed to evaluate the benefits of Lactobacillus plantarum (LP)-derived postbiotics on ameliorating Salmonella-induced neurological dysfunctions. Mice were pretreated with LP postbiotics (heat-killed bacteria or the metabolites) or active bacteria, and then challenged with Salmonella enterica Typhimurium (ST). Results showed that LP postbiotics, particularly the metabolites, effectively prevented ST infection in mice, as evidenced by the inhibited weight loss, bacterial translocation, and tissue damages. The LP postbiotics markedly suppressed brain injuries and neuroinflammation (the decreased interleukin (IL)-1β and IL-6, and the increased IL-4 and IL-10). Behavior tests indicated that LP postbiotics, especially the metabolites, protected mice from ST-induced anxiety and depressive-like behaviors and cognitive impairment. A significant modulation of neuroactive molecules (5-hydroxytryptamine, gamma-aminobutyric acid, brain-derived neurotrophic factor, dopamine, acetylcholine, and neuropeptide Y) was also found by LP postbiotic pretreatment. Microbiome analysis revealed that LP postbiotics optimized the cecal microbial composition by increasing Helicobacter, Lactobacillus and Dubosiella, and decreasing Mucispirillum, norank_f_Oscillospiraceae, and Eubacterium_siraeum_group. Moreover, LP postbiotics inhibited the reduction of short-chain fatty acids caused by ST infection. Pearson's correlation assays further confirmed the strong relationship of LP postbiotics-mediated benefits and gut microbiota. This study highlights the effectiveness of postbiotics and provide a promising strategy for preventing infection-induced brain disorders by targeting gut–brain axis.
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Affiliation(s)
- Yanping Wu
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
| | - Yan Wang
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
| | - Aixin Hu
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
| | - Xin Shu
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
| | - Wenxia Huang
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
| | - Jinsong Liu
- Zhejiang Vegamax Biotechnology Co., Ltd., Huzhou, China
| | - Baikui Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Ruiqiang Zhang
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
| | - Min Yue
- College of Animal Sciences, Zhejiang University, Hangzhou, China
| | - Caimei Yang
- College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China
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Hansen N. Immunopsychiatry – Innovative Technology to Characterize Disease Activity in Autoantibody-Associated Psychiatric Diseases. Front Immunol 2022; 13:867229. [PMID: 35711412 PMCID: PMC9197207 DOI: 10.3389/fimmu.2022.867229] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/19/2022] [Indexed: 01/04/2023] Open
Abstract
Background Anti-neural autoantibody-associated psychiatric disease is a novel field in immunopsychiatry that has been attracting attention thanks to its potentially positive therapeutic outcome and distinct prognosis compared with non-organic psychiatric disease. This review aims to describe recent novel technological developments for improving diagnostics in the field of autoantibody-related psychiatric disease.MethodsWe screened for relevant articles in PubMed for this narrative article. We focused on research methods such as neuroimaging, immune cells and inflammation markers, and molecular biomarkers in human biofluids like serum and cerebrospinal fluid and plasma proteomics.ResultsWe introduce several novel methods for investigating autoinflammation with the aim of optimizing therapies for autoantibody-associated psychiatric disease. We describe measuring the translocator protein 18kDa in activated microglia via positron emission tomography imaging, brain volumetric assessment, flow cell cytometry of cerebrospinal fluid and blood, and blood biological probes as well as psychopathological cues to help us gain insights into diagnosing inflammation and brain damage better in psychiatric patients presenting a suspected autoimmune etiology.ConclusionOur short methodological review provides an overview of recent developments in the field of autoantibody-related immunopsychiatry. More research is needed to prove their usefulness in diagnosing and treating autoantibody-associated psychiatric disease and its subtypes.
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Affiliation(s)
- Niels Hansen
- Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany
- Translational Psychoneuroscience, University Medical Center Göttingen, Göttingen, Germany
- *Correspondence: Niels Hansen,
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