The Chemokine CCL2 Protects Against Methylmercury Neurotoxicity

被引:30
作者
Godefroy, David [1 ]
Gosselin, Romain-Daniel [2 ,3 ]
Yasutake, Akira [4 ]
Fujimura, Masatake [5 ]
Combadiere, Christophe [6 ]
Maury-Brachet, Regine [7 ]
Laclau, Muriel [7 ]
Rakwal, Randeep [8 ]
Melik-Parsadaniantz, Stephane [9 ]
Bourdineaud, Jean-Paul [7 ]
Rostene, William [1 ]
机构
[1] Univ Paris 06, INSERM UMRS 968, Inst Vis, F-75012 Paris, France
[2] Univ Hosp Ctr, Dept Anesthesiol, Lausanne, Switzerland
[3] Univ Lausanne, Lausanne, Switzerland
[4] Kumamoto Univ, Grad Sch Med, Kumamoto 8608555, Japan
[5] Natl Inst Minamata Dis, Dept Basic Med Sci, Minamata, Kumamoto, Japan
[6] Univ Paris 06, INSERM UMRS 543, Hop Pitie Salpetriere, F-75013 Paris, France
[7] Univ Bordeaux 1, CNRS UMR 5805, Stn Marine Arcachon, F-33120 Arcachon, France
[8] Showa Univ, Sch Med, Shinagawa Ku, Tokyo 1428555, Japan
[9] Univ Paris 06, INSERM UMRS 975, Hop Pitie Salpetriere, F-75013 Paris, France
关键词
methylmercury neurotoxicity; chemokines; CCL2/CCR2; fish diet; neuroprotection; microglia; neuronal cell death; OXIDATIVE STRESS; NEURONAL EXPRESSION; MERCURY EXPOSURE; CELL-DEATH; RAT-BRAIN; LOW-LEVEL; GLUTATHIONE; TOXICITY; MICE; NEUROTRANSMITTERS;
D O I
10.1093/toxsci/kfr252
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:209 / 218
页数:10
相关论文
共 43 条
[1]  
[Anonymous], 1971, Statistical Principles in Experimental Design
[2]   Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity [J].
Aschner, M. ;
Syversen, T. ;
Souza, D. O. ;
Rocha, J. B. T. ;
Farina, M. .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2007, 40 (03) :285-291
[3]   Low-level methylmercury exposure as a risk factor for neurologic abnormalities in adults [J].
Auger, N ;
Kofman, O ;
Kosatsky, T ;
Armstrong, B .
NEUROTOXICOLOGY, 2005, 26 (02) :149-157
[4]   Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain:: Functional effect of MCP-1/CCL2 on calcium mobilization in primary cultured neurons [J].
Banisadr, G ;
Gosselin, RD ;
Mechighel, P ;
Rostène, W ;
Kitabgi, P ;
Parsadaniantz, SM .
JOURNAL OF COMPARATIVE NEUROLOGY, 2005, 492 (02) :178-192
[5]   Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain:: Evidence for its colocalization with neurotransmitters and neuropeptides [J].
Banisadr, G ;
Gosselin, RD ;
Mechighel, P ;
Kitabgi, P ;
Rosène, W ;
Parsadaniantz, SPM .
JOURNAL OF COMPARATIVE NEUROLOGY, 2005, 489 (03) :275-292
[6]   Deleterious effects in mice of fish-associated methylmercury contained in a diet mimicking the Western populations' average fish consumption [J].
Bourdineaud, Jean-Paul ;
Fujimura, Masatake ;
Laclau, Muriel ;
Sawada, Masumi ;
Yasutake, Akira .
ENVIRONMENT INTERNATIONAL, 2011, 37 (02) :303-313
[7]   Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians [J].
Bourdineaud, Jean-Paul ;
Bellance, Nadege ;
Benard, Giovani ;
Brethes, Daniel ;
Fujimura, Masatake ;
Gonzalez, Patrice ;
Marighetto, Aline ;
Maury-Brachet, Regine ;
Mormede, Cecile ;
Pedron, Vanessa ;
Philippin, Jean-Nicholas ;
Rossignol, Rodrigue ;
Rostene, William ;
Sawada, Masumi ;
Laclau, Muriel .
ENVIRONMENTAL HEALTH, 2008, 7 (1)
[8]   Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344 [J].
Brodmerkel, CM ;
Huber, R ;
Covington, M ;
Diamond, S ;
Hall, L ;
Collins, R ;
Leffet, L ;
Gallagher, K ;
Feldman, P ;
Collier, P ;
Stow, M ;
Gu, XM ;
Baribaud, F ;
Shin, N ;
Thomas, B ;
Burn, T ;
Hollis, G ;
Yeleswaram, S ;
Solomon, K ;
Friedman, S ;
Wang, AL ;
Xue, CB ;
Newton, RC ;
Scherle, P ;
Vaddi, K .
JOURNAL OF IMMUNOLOGY, 2005, 175 (08) :5370-5378
[9]   Neuroprotective activity of chemokines against N-methyl-D-aspartate or β-amyloid-induced toxicity in culture [J].
Bruno, V ;
Copani, A ;
Besong, G ;
Scoto, G ;
Nicoletti, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2000, 399 (2-3) :117-121
[10]   Mechanisms and modulation of neural cell damage induced by oxidative stress [J].
Ceccatelli, Sandra ;
Tamm, Christoffer ;
Zhang, Qing ;
Chen, Ming .
PHYSIOLOGY & BEHAVIOR, 2007, 92 (1-2) :87-92