Developmental lead exposure alters gene expression of metabotropic glutamate receptors in rat hippocampal neurons.
Exposure to lead in utero and in infancy is associated with a risk of impaired cognitive development. Increasing evidence suggests that the family of metabotropic glutamate receptors (mGluRs) plays an important role in synaptic plasticity and memory formation. We determined whether mGluRs subtypes 1, 3, and 7 (mGluR1, mGluR3, and mGluR7) were involved in developmental neurotoxicity due to lead. Embryonic rat hippocampal neurons were cultured for 21 days and exposed to lead chloride beginning on the fourth day of incubation. We investigated levels of mGluR1, mGluR3, and mGluR7 mRNA expression by using quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) with lead exposure at 10 nM, 1 microM, and 100 microM. Lead exposure in vitro downregulated the expression of mGluR1 mRNA and upregulated the expression of mGluR3 and mGluR7 mRNA in a dose-dependent manner. We speculate that mGluRs may be involved in lead neurotoxicity. Pathways that likely contribute to lead neurotoxicity by means of mGluRs are impairment of long-term potentiation, effects on N-methyl-D-aspartate (NMDA) receptor functions, and depotentiation.
Xu
Jian
J
Shanghai XinHua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai Key Laboratory of Children's Environmental Health, Shanghai 200092, China.
Yan
Chong-Huai
CH
Wu
Sheng-Hu
SH
Yu
Xiao-Dan
XD
Yu
Xiao-Gang
XG
Shen
Xiao-Ming
XM
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D007854:Lead / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D007854:Lead; C029891:lead chloride