Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression
Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression
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DOI：
10.1046/j.0953-816x.2001.01685.x
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发表时间：
2001-08-01
影响因子：
3.4
通讯作者：
Vreugdenhil, E
中科院分区：
文献类型：
--
作者：
Datson, NA;van der Perk, J;Vreugdenhil, E
肾上腺皮质类固醇(CORT)对海马体的功能有深远的影响。这是由盐皮质激素(MR)和糖皮质激素受体(GR)通过激活或抑制靶基因而以协调的方式介导的。本研究的目的是利用基因表达序列分析(SAGE)技术，鉴定MR和/或GR调节的皮质激素反应的海马区基因。对不同皮质醇暴露条件下的SAGE图谱进行了比较，鉴定出203个皮质醇反应基因，它们参与许多不同的细胞过程，如能量消耗和细胞代谢；蛋白质合成和周转；信号转导和神经元连接和神经传递。除了之前发现的一些皮质醇反应基因外，本研究中发现的大多数基因都是新基因。原位杂交显示，随机选择的六个皮质醇反应基因在海马神经元中有不同的表达模式。此外，通过原位杂交，我们证实了这六个基因确实受CORT的调控，从而强调了SAGE数据的有效性。MR和GR依赖的表达谱比较表明，大多数CORT反应基因要么受激活的MR调控，要么受激活的GR调控，只有少数基因同时对激活的MR和GR有反应。这表明，激活的MR和GR的不同效应的分子基础是激活或抑制不同但部分重叠的基因集。这些假定的皮质醇反应基因将提供对MR和GR对神经元兴奋性、记忆形成和行为的不同甚至有时相反影响的分子机制的洞察，以及它们在神经元保护和损伤中的作用。
Adrenal corticosteroids (CORT) have a profound effect on the function of the hippocampus. This is mediated in a coordinated manner by mineralocorticoid (MR) and glucocorticoid receptors (GR) via activation or repression of target genes. The aim of this study was to identify, using serial analysis of gene expression (SAGE), CORT-responsive hippocampal genes regulated via MR and/or GR. SAGE profiles were compared under different conditions of CORT exposure, resulting in the identification of 203 CORT-responsive genes that are involved in many different cellular processes like, energy expenditure and cellular metabolism; protein synthesis and turnover; signal transduction and neuronal connectivity and neurotransmission. Besides some previously identified CORT-responsive genes, the majority of the genes identified in this study were novel. In situ hybridization revealed that six randomly chosen CORT-responsive genes had distinct expression patterns in neurons of the hippocampus. In addition, using in situ hybridization, we confirmed that these six genes were indeed regulated by CORT, underscoring the validity of the SAGE data. Comparison of MR- and GR-dependent expression profiles revealed that the majority of the CORT-responsive genes were regulated either by activated MR or by activated GR, while only a few genes were responsive to both activated MR and GR. This indicates that the molecular basis for the differential effects of activated MR and GR is activation or repression of distinct, yet partially overlapping sets of genes. The putative CORT-responsive genes identified here will provide insight into the molecular mechanisms underlying the differential and sometimes opposing effects of MR and GR on neuronal excitability, memory formation and behaviour as well as their role in neuronal protection and damage.