环磷腺苷效应元件结合蛋白（CREB）具有调节神经元再生和突触形成的功能，在抑郁症发生发展过程中起着重要作用。以往研究主要集中于CREB表达及CREB磷酸化水平与抑郁症发病机制和治疗的相关性，而CREB在介导抗抑郁药物作用中如何调控靶基因从而影响突触可塑性的机制并不清楚。我们前期研究发现CREB通过调节脑源性神经生长因子（BDNF）的表达参与越鞠丸快速抗抑郁作用。本项目拟采用染色质免疫共沉淀-测序（ChIP-Seq）技术鉴定小鼠海马组织中CREB在全基因组上的DNA结合位点；同时，结合基因芯片分析的表达谱信息，筛选与越鞠丸快速抗抑郁作用相关联的CREB靶基因；进一步，结合RNA干扰、行为学方法检测，验证CREB靶基因在越鞠丸快速抗抑郁中的作用。所得研究结果不仅可以获得新的CREB靶基因，有助于我们更好地理解CREB介导越鞠丸快速抗抑郁作用的分子机制，还可以为抑郁症的基因治疗提供新的理论基础。

cAMP-response element binding protein (CREB) has the functions of regulating neuron regeneration and synapse formation and plays an important role in the process of depression occurrence and development. Previous studies mainly focused on the relations of CREB expression and CREB phosphorylation with depression mechanism and treatment. CREB regulates target genes and influences synaptic plasticity in mediating antidepressant effects, but the mechanism is unclear. In previous study, we found that CREB involved in the rapid antidepressant effect of Yueju by regulating the expression of brain-derived neurotrophic factor (BDNF). This project is planned to adopt Chromatin Immunoprecipitation Sequencing (ChIP-Seq) to drawing the accurate DNA-binding profile of transcription factor CREB. Combined with the expression profile information analyzed by gene chip, we will identify target genes regulated by CREB in hippocampus of mice, which are related to rapid antidepressant effect of Yueju. Furthermore, with using RNAi and behavioral detection methods, we will validate the influence of CREB target genes on rapid antidepressant effect of Yueju. The results not only obtain new CREB target genes, which help us to better understand the molecular mechanism of rapid antidepressant effect of Yueju mediated by CREB, but also provide new theoretical basis for gene therapy of depression.