DNMT3a调节CRMP2DNA甲基化介导小鼠抑郁样行为的机制研究

作为一种严重的精神疾病，抑郁症具有高发病率、高自杀率的特点，给个人和社会带来严重负担。抑郁症是一种多因素疾病，由遗传因素及环境因素相互作用所导致。目前的证据表明CRMP2参与神经可塑性介导抑郁症的发生。然而，CRMP2作用的具体调控机制尚不清楚。既往研究表明DNA甲基化作为最稳定的表观遗传学方式参与抑郁症的发生。应激环境可导致表观遗传学改变，调节DNA转录功能，在抑郁症的发病机制中发挥关键作用。本团队既往研究结果表明，DNMT3a调控CRMP2基因启动子区DNA甲基化水平，从而影响CRMP2的表达，参与抑郁症的发病机制。根据既往的研究及我们前期的研究结果，本项目拟从动物水平及细胞水平进行深入研究，探讨DNMT3a调控CRMP2 DNA甲基化参与神经可塑性介导抑郁症发生的具体机制，为抑郁症的发病机制提供新的理论依据，为抑郁症的诊疗提供潜在的生物学靶点及新思路。

As a severe psychiatric disorder, depression is characterized by high morbidity and suicide rate, with an enormous burden for patients and for society. Depression is a multifactorial illness that is guided by the interaction between genetic susceptibility and environmental stimuli. Current evidence supports the idea that CRMP2 is involved in the pathogenesis of depression by regulating the neuroplasticity. However, the regulatory mechanisms underlying the role of CRMP2 remain unclear. Epigenetic mechanisms can modulate DNA transcriptional functionality in response to the environment and play a critical role in the processes that contribute to the pathophysiology of depression. In our previous study, the results demonstrated that DNMT3a regulates the level of DNA methylation in the CRMP2 gene promoter region, thus affecting the expression of CRMP2 and participating in the pathogenesis of depression. According to the previous research and our previous research results, we plan to elucidate the neuropathological mechanism of CRMP2 in stress-induced depression by studying the animal level, molecular level and cellular level. To provide a new theoretical basis for the pathogenesis of depression, potential biological targets and new ideas for the treatment of depression.