慢性应激与基因相互作用导致抑郁的发病。研究表明，应激能够改变前额叶皮层中基因转录水平，从而引起神经元突触和结构可塑性改变诱发抑郁的产生。但慢性应激调控神经元基因转录的分子机制仍不清楚。在前期研究中，申请人从表观遗传学角度出发，发现慢性应激特异性的上调前额叶皮层中表观遗传因子CDYL（Chromodomain Y-like protein）的表达水平。CDYL上调增加抑郁的易感性，而下调降低抑郁易感性。Chip-sequencing和生物信息学研究结果显示，CDYL下游靶基因能够调控神经元的突触和结构可塑性的形成，因此申请人提出“慢性应激导致的前额叶中CDYL表达升高，通过抑制基因转录介导前额叶神经元的突触可塑性和结构可塑性形成，从而导致抑郁症发生和发展”的科学假设。本研究拟从行为、神经网络、神经元、分子不同层次揭示CDYL在抑郁发生和发展中的作用，为抑郁的预防和治疗提供新思路。

Dysregulation of synaptic and structural plasticity is implicated in a range of psychiatric disorders such as depression. However, the molecular mechanism underlying the process of depression remains poorly understood. OurpPreliminary data showed that the transcription corepressor chromodomain Y-like (CDYL) protein is a critical regulator of the development of depression. In this study, we will use that chronic social defeat stress model and unpredictable chronic mild stress model, to assess the CDYL expression in the depression-related brain area. In addition, we will assess the relationship between the increase in CDYL expression and depression susceptibility. We will also perform the comparative RNA-seq experiments to identify CDYL downstream target genes and their correlation with depression. Present study will provide a detail the mechanism by which how epigenetic "Reader" protein affect the plasticity, this contribute the development of depression. It will uncover a potential therapeutic target for major depressive disorder.