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首页> 外文期刊>The European Journal of Neuroscience >Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression.
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Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression.

机译：使用基因表达序列分析鉴定大鼠海马中的皮质类固醇反应性基因。

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摘要

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.
机译：肾上腺皮质类固醇（CORT）对海马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以协调的方式介导的。这项研究的目的是利用基因表达的系列分析（SAGE），确定通过MR和/或GR调节的CORT反应性海马基因。在不同的CORT暴露条件下比较了SAGE概况，从而鉴定了203个CORT响应基因，这些基因参与了许多不同的细胞过程，例如能量消耗和细胞代谢。蛋白质合成和周转;信号转导，神经元连通性和神经传递。除了一些先前确定的CORT反应基因外，本研究中鉴定的大多数基因都是新颖的。原位杂交表明，六个随机选择的CORT反应基因在海马神经元中具有不同的表达模式。此外，使用原位杂交，我们证实了这六个基因确实受CORT调控，从而强调了SAGE数据的有效性。 MR和GR依赖的表达谱的比较表明，大多数CORT响应基因受激活的MR或受激活的GR调控，而只有少数基因对激活的MR和GR都有响应。这表明激活的MR和GR的差异作用的分子基础是不同基因组（部分重叠）的激活或抑制。此处鉴定出的假定的CORT反应基因将提供有关MR和GR对神经元兴奋性，记忆形成和行为的差异性（有时是相反的）作用的分子机制的深刻见解，以及它们在神经元保护和损伤中的作用。

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