1. The chemokine CCL2 protects against methylmercury neurotoxicity.: chemokines and methymercury neurotoxicity
- Author
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Jean-Paul Bourdineaud, Romain-Daniel Gosselin, Stéphane Mélik-Parsadaniantz, Randeep Rakwal, Muriel Laclau, William Rostène, Akira Yasutake, David Godefroy, Régine Maury-Brachet, Christophe Combadière, Masatake Fujimura, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pain Research Unit, Université de Lausanne = University of Lausanne (UNIL), Department of Basic Medical Science, National Institute for Minamata Disease, Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Showa University, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 'Sante'-environnement et sante'-travail' program, ANR no. SEST 2005-034, University P and M. Curie Paris VI for France-Japan exchanges., ANR-05-SEST-0034,Effets du mercure sur la santé des écosystèmes aquatiques et des populations humaines(2005), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lausanne (UNIL), and Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)
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MESH: Cell Death ,Male ,CCR2 ,Time Factors ,MESH: Neurons ,Cell Culture Techniques ,microglia ,Gene Expression ,chemokines ,Toxicology ,MESH: Mice, Knockout ,MESH: Dose-Response Relationship, Drug ,Mice ,0302 clinical medicine ,methylmercury neurotoxicity ,Premovement neuronal activity ,MESH: Animals ,Tissue Distribution ,MESH: Superoxide Dismutase ,Cells, Cultured ,Chemokine CCL2 ,Mercury Poisoning, Nervous System ,Mice, Knockout ,Neurons ,0303 health sciences ,Cell Death ,Microglia ,Chemistry ,Brain ,Methylmercury Compounds ,3. Good health ,medicine.anatomical_structure ,MESH: Environmental Pollutants ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,neuroprotection ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Environmental Pollutants ,fish diet ,Neuron death ,MESH: Cells, Cultured ,MESH: Methylmercury Compounds ,medicine.medical_specialty ,Programmed cell death ,MESH: Gene Expression ,Neurotransmission ,Neuroprotection ,MESH: Brain ,03 medical and health sciences ,neuronal cell death ,MESH: Mice, Inbred C57BL ,Internal medicine ,medicine ,Animals ,MESH: Tissue Distribution ,MESH: Mice ,MESH: Chemokine CCL2 ,030304 developmental biology ,MESH: Cell Culture Techniques ,Dose-Response Relationship, Drug ,Superoxide Dismutase ,MESH: Mercury Poisoning, Nervous System ,MESH: Time Factors ,Neurotoxicity ,CCL2/CCR2 ,medicine.disease ,[SDE.ES]Environmental Sciences/Environmental and Society ,MESH: Male ,Mice, Inbred C57BL ,Endocrinology ,13. Climate action ,Immunology ,030217 neurology & neurosurgery - Abstract
10, 5 figures, 3 tables, 1 suppl figure and 1 suppl table; International audience; Industrial pollution due to heavy metals such as mercury is a major concern for the environment and public health. Mercury, in particular methylmercury (MeHg), primarily affects brain development and neuronal activity, resulting in neurotoxic effects. Because chemokines can modulate brain functions and are involved in neuroinflammatory and neurodegenerative diseases, we tested the possibility that the neurotoxic effect of MeHg may interfere with the chemokine CCL2. We have used an original protocol in young mice using a MeHg-contaminated fish-based diet for 3 months relevant to human MeHg contamination. We observed that MeHg induced in the mice cortex a decrease in CCL2 concentrations, neuronal cell death, and microglial activation. Knock-out (KO) CCL2 mice fed with a vegetal control food already presented a decrease in cortical neuronal cell density in comparison with wild-type animals under similar diet conditions, suggesting that the presence of CCL2 is required for normal neuronal survival. Moreover, KO CCL2 mice showed a pronounced neuronal cell death in response to MeHg. Using in vitro experiments on pure rat cortical neurons in culture, we observed by blockade of the CCL2/CCR2 neurotransmission an increased neuronal cell death in response to MeHg neurotoxicity. Furthermore, we showed that sod genes are upregulated in brain of wild-type mice fed with MeHg in contrast to KO CCL2 mice and that CCL2 can blunt in vitro the decrease in glutathione levels induced by MeHg. These original findings demonstrate that CCL2 may act as a neuroprotective alarm system in brain deficits due to MeHg intoxication.
- Published
- 2011
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