The role of metabotropic glutamate receptor 5 in developmental lead neurotoxicity.
A complete explanation of the mechanisms of lead-induced developmental neurotoxicity remains unknown. The glutamate receptor is one of the most important targets of lead. More recently, metabotropic glutamate receptor 5 (mGluR5) has been shown to have a functional relationship with learning and memory. We investigated the impact of developmental lead exposure on hippocampal mGluR5 expression and its potential role in lead neurotoxicity. Both in vitro model of lead exposure with Pb(2+) concentrations of 0, 10 nM, 1 microM, and 100 microM in cultured rat embryonic hippocampal neurons, and the in vivo model of rat maternal lead exposure involving both gestational and lactational exposure with 0, 0.05%, 0.2%, and 0.5% lead acetate were utilized. Immunoperoxidase and immunofluorescent analyses, quantitative PCR and western blotting were used. In vitro studies revealed that expression of mGluR5 mRNA and protein was decreased dose-dependently after lead exposure, which was further confirmed by the results of in vivo studies. These data suggest that mGluR5 might be involved in lead-induced neurotoxicity by disturbing mGluR5-induced long-term depression and decreasing N-methyl-D-aspartic acid receptor (NMDAR)-dependent or protein synthesis-dependent long-term potentiation. These results might improve the understanding of the mechanism and potential treatments for moderate to severe lead poisoning in children.
Xu
Jian
J
Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai Key Laboratory of Children's Environmental Health, 1665 Kong Jiang Road, Shanghai 200092, China.
Yan
Chong-huai
CH
Yang
Bo
B
Xie
Han-fang
HF
Zou
Xiang-yu
XY
Zhong
Le
L
Gao
Yu
Y
Tian
Ying
Y
Shen
Xiao-ming
XM
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000473:pathology; D007124:Immunoenzyme Techniques; D007774:Lactation; D007854:Lead / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity; D020263:Lead Poisoning, Nervous System / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D007854:Lead; D012313:RNA