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The chemokine CCL2 protects against methylmercury neurotoxicity.
Godefroy D., Gosselin R.-D., Yasutake A., Fujimura M., Combadière C., Maury-Brachet R., Laclau M. N., Rakwal R., Melik-Parsadaniantz S., Bourdineaud J.-P. et al
Review of Economic Dynamics 125, 1 (2012) 209-18 - http://www.hal.inserm.fr/inserm-00630697
(21976372)
The chemokine CCL2 protects against methylmercury neurotoxicity.
David Godefroy1, Romain-Daniel Gosselin2, Akira Yasutake3, Masatake Fujimura3, Christophe Combadière4, Régine Maury-Brachet5, Muriel Laclau5, Randeep Rakwal6, Stéphane Melik-Parsadaniantz7, Jean-Paul Bourdineaud5, William Rostène () 1
1 :  Institut de la vision
INSERM : U968 – CNRS : UMR7210 – Université Pierre et Marie Curie (UPMC) - Paris VI : UM80
France
2 :  Pain Research Unit
Université de Lausanne
Department of Anesthesiology and Department of Cell Biology and Morphology, University Hospital Center and University of Lausanne, Lausanne
Suisse
3 :  Department of Basic Medical Science
National Institute for Minamata Disease
Minamata City, Kumamoto
Japon
4 :  Immunologie cellulaire et tissulaire
http://sirius.cervi.chups.jussieu.fr
INSERM : U543 – IFR113 – Université Pierre et Marie Curie (UPMC) - Paris VI
Gh Pitie-Salpetriere 83, Boulevard de L'Hopital 75013 PARIS
France
5 :  EPOC - Environnements et Paléoenvironnements OCéaniques
http://www.epoc.u-bordeaux.fr
CNRS : UMR5805 – INSU – Université Sciences et Technologies - Bordeaux I – École Pratique des Hautes Études [EPHE] – Observatoire Aquitain des Sciences de l'Univers
Avenue des Facultés - 33405 TALENCE CEDEX
France
6 :  Showa University
Showa University
Japon
7 :  CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
http://www.cricm.upmc.fr/
INSERM : U975 – Université Pierre et Marie Curie (UPMC) - Paris VI – CNRS : UMR7225
GHU Pitié-Salpêtrière 47, boulevard de l'Hôpital 75651 Paris cedex 13
France
chemokines and methymercury neurotoxicity
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.
Sciences du Vivant/Neurosciences
Sciences de l'environnement/Environnement et Société
Sciences du Vivant/Toxicologie
Anglais
1094-2025

Articles dans des revues avec comité de lecture
10.1093/toxsci/kfr252
Review of Economic Dynamics
Publisher Elsevier
ISSN 1094-2025 (eISSN : 1096-0929)
internationale
01/2012
05/10/2011
125
1
209-18

methylmercury neurotoxicity – chemokines – CCL2/CCR2 – fish diet – neuroprotection – microglia – neuronal cell death.
Animals – Brain – Cell Culture Techniques – Cell Death – Cells – Cultured – Chemokine CCL2 – Dose-Response Relationship – Drug – Environmental Pollutants – Gene Expression – Male – Mercury Poisoning – Nervous System – Methylmercury Compounds – Mice – Inbred C57BL – Knockout – Neurons – Superoxide Dismutase – Time Factors – Tissue Distribution
10, 5 figures, 3 tables, 1 suppl figure and 1 suppl table
''Sante'-environnement et sante'-travail'' program, ANR no. SEST 2005-034; University P and M. Curie Paris VI for France-Japan exchanges.
Référence du projet SEST-034
Année 2005
Titre du projet Effets du mercure sur la santé des écosystèmes aquatiques et des populations humaines
Intitulé Programme Santé-environnement et Santé-travail
Acronyme de l'appel SEST
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