Nongenomic effects of corticosterone on NMDA receptor-mediated current in cultured embryonic 18d rat hippocampal neurons
会议名称：《中国神经科学学会第四次会员代表大会暨第八届全国学术会议》
会议日期：2009年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词：stress corticosterone N-mentyl-D-aspartate receptor nongenomic
摘 要：Objective Glucocorticoids(Gc),main stress hormone,has been shown to modulate synaptic plasticity and the process of learning and memory in *** exerts long-term effects on central nervous system(CNS) through classical *** is increasing evidence for rapid Gc actions triggered by the activation of membrane-associated receptors and nongenomic signaling *** N-mentyl-D-aspartate(NMDA) receptor plays a pivotal role in a variety of physiological processes in the CNS,including LTP,with involvement in learning and ***, nongenomic effects of Gc on N-mentyl-D-aspartate(NMDA) receptor,the key receptor for synaptic plasticity,remain *** Whole-cell patch-clamp was performed on primary cultured E18 hippocampal *** PLC-β3 was measured by Western *** cAMP content was measured by RIA ***(1) Primary cultured embryonic hippocampal neurons were deficient in glucocorticoid *** corticosterone(B)(10-7 mol/L) and BSA-conjugated corticosterone(B-BSA)(10-7 mol/L) elicited a rapid depression of NMDA-induced currents in a dose-dependent *** effect was reversed by the G-protein antagonist(GDP-β-S),but not by glucocorticoid receptor antagonist(Ru38486) or mineralocorticoid receptor antagonist(spironolactone).(2) Investigations on the signaling pathways of B showed that B dose-dependently induced phosphorylated PLC-βexpression and increased intracellular cAMP content in these cells.(3) Blocking protein kinase A(H89) and adenylate cyclase(SQ 22536) partly abolished the Binduced depression of NMDA current.(4) Application of inhibitor of phospholipase C(U73122),IP3 receptor antagonist (2APB),Ca chelator(BAPTA) and protein kinase C inhibitor(chelerythrine) prevented B-induced depression of NMDA current.(5) Application of inhibitors of JNK(SP600125) and p38 MAPKs(SB202190) prevented B-induced depression of NMDA current,whereas blocking ERK activity failed to do the *** results sug