LncRNA调控CREB对抑郁症作用机理研究

项目名称： LncRNA调控CREB对抑郁症作用机理研究

项目编号： No.81471379

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张克让

作者单位： 山西医科大学

项目金额： 85万元

中文摘要： 抑郁症病因不明是导致其治疗及预后差的主要原因，神经细胞信号转导通路异常造成的神经可塑性障碍为抑郁症最重要的病因之一。研究表明，神经细胞信号转导通路关键节点CREB表达异常影响神经可塑性并参与了抑郁症发病。然而，迄今为止，抑郁症中CREB表达调控机制仍不清楚，课题组前期通过芯片筛查、生物信息学分析和qRT-PCR验证，发现抑郁症中长链非编码RNA（lncRNA）CREB1/2可调控CREB表达。据此提出lncRNA CREB1/2通过调控CREB影响神经可塑性参与抑郁症发病的科学假说。本课题拟采用人体、动物、细胞水平研究，深入探讨：（1）lncRNA CREB1/2对CREB的调控作用；（2）lncRNA CREB1/2对CREB的调控作用影响神经可塑性参与抑郁症发病。本项目将发现抑郁症神经可塑性新的影响因素，补充完善抑郁症神经可塑性障碍假说的内容，也为抗抑郁药物的研发提供新线索。

中文关键词： 抑郁症；神经可塑性；长链非编码RNA；cAMP反应元件结合蛋白

英文摘要： The etiology of Major depressive disorder (MDD) remains unknown, which may lead to poor effect and prognosis. It is gradually recognized that the abnormal signal transduction pathway of neruon may block the neuroplasticity and is very likely to be involved in the pathophysiology of MDD. A growing body of studies has provided evidence that the abnormal expression regulation of CREB, the key node in neuron signal transduction pathway may participate in the pathogenesis of MDD by affecting the neuroplasticity. However the regulatory mechanism of CREB in MDD remains unclear. With the help of gene chip screening, bioinformatics analysis and qRT-PCR verification, our preliminary study found that lncRNA CREB1/2 can modulate the expression of CREB in MDD. According to this, we proposed the hypothesis thatlncRNA CREB1/2 impacts the neuroplasticity and participates in the pathogenesis of depression by regulating CREB. This study attempts to explore the following questions deeply on human body, animal and cellular levels.(1)The regulation of LncRNA CREB1/2 on CREB. (2) The CREB regulated by LncRNA CREB1/2 may impact the neuroplasticity and participate in the pathogenesis of MDD. These ?ndings may contribute to illuminating new influence factor of neuroplasticity in MDD, supplementing the hypothises of neuroplasticity in MDD and providing clues for new antidepressants development.

英文关键词： Major Depressive Disorder(MDD);Neuroplasticity;Long noncoding RNA(LncRNA);cAMP presponse elementbinding protein(CREB)