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。

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 that"lncRNA 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.