The chemokine CCL2 protects against methylmercury neurotoxicity

Autor: Godefroy, David, Gosselin, Romain-Daniel, Yasutake, Akira, Fujimura, Masatake, Combadière, Christophe, Maury-Brachet, Régine, Laclau, Muriel, Rakwal, Randeep, Melik-Parsadaniantz, Stéphane, Bourdineaud, Jean-Paul, Rostène, William
Přispěvatelé: Institut de la Vision, 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), Pain Research Unit, Université de 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-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), 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), 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), '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)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Review of Economic Dynamics
Review of Economic Dynamics, Elsevier, 2012, 125 (1), pp.209-18. ⟨10.1093/toxsci/kfr252⟩
ISSN: 1094-2025
1096-0929
DOI: 10.1093/toxsci/kfr252⟩
Popis: 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.
Databáze: OpenAIRE
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