Stress induced hippocampal mineralocorticoid and estrogen receptor beta gene expression and long-term potentiation in male adult rats is sensitive to early-life stress experience

摘要

Glucocorticoid hormones and their receptors have been identified to be involved in emotional and cognitive disorders in early stressed subjects during adulthood. However, the impact of other steroid hormones and receptors has been considered less. Especially, functional roles of estrogen and estrogen receptors in male subjects are largely unknown. Therefore, we measured hippocampal concentrations of 17 beta-estradiol, corticosterone and testosterone, as well as the gene expression of estrogen receptor alpha and beta (ER alpha, beta), androgen receptor (AR), glucocorticoid (GR) and mineralocorticoid (MR) receptors after stress in adulthood in maternally separated (MS+; at postnatal days 14-16 for 6 h each day) and control (MS-) male rats. In vivo hippocampal long-term potentiation (LTP) serves as a cellular model of learning and memory formation. Population spike- (PSA) and the fEPSP-LTP within the dentate gyrus (DG) were reinforced by elevated-platformstress (EP-stress) in MS- but not in MS+ rats. MR- and ER beta-mRNA were upregulated 1 h after EP-stress in MS- but not in MS+ rats as compared to non-stressed littermates. Infusion of an MR antagonist before LIP induction blocked early- and late-PSA- and -fEPSP-LTP, whereas blockade of ER B impaired only the late PSA-LTP. Application of a DNA nnethyltransferase (DNMT) inhibitor partly restored the LTP-reinforcement in MS+ rats, accompanied by a retrieval of ER beta- but not MR-mRNA upregulation. Basal ER beta gene promoter methylation was similar between groups, whereas MS+ and MS rats showed different methylation patterns across CpG sites after EP-stress. These findings indicate a key role of ER beta in early-stress mediated emotionality and emotion-induced late-LIP in adult male rats via DNA rnethylation mechanisms. (C) 2012 Elsevier Ltd. All rights reserved.