Aberrant REST-mediated transcriptional regulation in major depressive disorder
Aberrant REST-mediated transcriptional regulation in major depressive disorder
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DOI：
10.1016/j.jpsychires.2009.09.009
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发表时间：
2010-04-01
影响因子：
4.8
通讯作者：
Watanabe, Yoshifumi
中科院分区：
文献类型：
--
作者：
Otsuki, Koji;Uchida, Shusaku;Watanabe, Yoshifumi
越来越多的证据表明，异常转录调控是心境障碍病理生理学的关键组成部分之一。抑制因子-1沉默转录因子(REST)是含有抑制因子-1(RE-1)结合位点的基因的负调控因子。REST有许多靶基因，包括促肾上腺皮质激素释放激素(CRH)、脑源性神经营养因子、5-羟色胺1A受体，这些基因被认为参与了抑郁症的病理生理和抗抑郁药物的作用。然而，休息介导的转录调控在情绪障碍中的潜在作用仍不清楚。在这项研究中，我们用实时定量聚合酶链式反应检测了处于抑郁和缓解期的抑郁症和双相情感障碍患者外周血细胞中REST及其已知和推测的靶基因的mRNA水平。我们发现重度抑郁障碍患者的REST基因表达降低，CRH、腺苷环化酶5和肿瘤坏死因子超家族成员12-13的基因表达增加，患者处于抑郁状态，但没有缓解状态。在双相情感障碍患者中未发现这些mRNAs的表达改变。我们的结果提示，至少CRH、腺苷环化酶5和肿瘤坏死因子超家族成员12-13的REST介导的转录调控的异常可能是状态依赖的，并与抑郁症的病理生理有关。(C)2009爱思唯尔有限公司。保留所有权利。
There is growing evidence that aberrant transcriptional regulation is one of the key components of the pathophysiology of mood disorders. The repressor element-1 silencing transcription factor (REST) is a negative regulator of genes that contain the repressor element-1 (RE-1) binding site. REST has many target genes, including corticotropin releasing hormone (CRH), brain-derived neurotrophic factor, serotonin 1A receptor, which are suggested to be involved in the pathophysiology of depression and the action of antidepressants. However, a potential role for REST-mediated transcriptional regulation in mood disorders remains unclear. In this study, we examined the mRNA levels of REST and its known and putative target genes, using quantitative real-time PCR in peripheral blood cells of patients with major depressive and bipolar disorders in both a current depressive and a remissive state. We found reduced mRNA expression of REST and increased mRNA expression of CRH, adenylate cyclase 5, and the tumor necrosis factor superfamily, member 12-13 in patients with major depressive disorder in a current depressive state, but not in a remissive state. Altered expression of these mRNAs was not found in patients with bipolar disorder. Our results suggest that the aberrant REST-mediated transcriptional regulation of, at least, CRH, adenylate cyclase 5, and tumor necrosis factor superfamily, member 12-13, might be state-dependent and associated with the pathophysiology of major depression. (C) 2009 Elsevier Ltd. All rights reserved.