内侧前额叶皮层miR-129-5p在CMS大鼠抑郁样行为发生中的作用及机制研究

抑郁症是一种严重的精神障碍性疾病，给个人、社会和家庭造成沉重的负担，然而其发病机制仍不清楚。miR-129-5p在人、小鼠和大鼠中序列完全保守，在中枢神经系统的发育中起到重要的调节作用。我们前期研究发现miR-129-5p在慢性温和应激（CMS）抑郁模型大鼠的内侧前额叶皮层（mPFC）表达升高，同时还发现在正常大鼠mPFC表达miR-129-5p可诱导大鼠产生抑郁样行为。上述实验结果提示miR-129-5p对抑郁的发生具有重要的调节作用。因此，本项目将在前期工作基础上，综合运用分子生物学、形态学、神经环路示踪标记、光纤记录、化学遗传学、光遗传学及动物行为学等多种技术方法，分别从神经可塑性及神经环路层面探讨miR-129-5p在CMS大鼠抑郁样行为发生中的作用及相关的神经生物学机制，该研究不仅能进一步丰富抑郁症的发病机制，也可为抑郁症的诊断和治疗提供新的线索和资料。

Depression is serious psychiatric disorder which results in a heavy burden on individuals, families and society. However, the pathological mechanisms underlying depression is still unclear. The miR-129-5p, as a kind of non-coding RNA, is highly conserved in human, mouse and rat. It has been reported that miR-129-5p plays an important role in regulation of central nervous development. Our recent study showed that the level of miR-129-5p was increased in the medial prefrontal cortex (mPFC) of chronic mild stress (CMS) rats. Meanwhile, overexpression of miR-129-5p in the mPFC of normal rats induced depression-like behaviours. All above findings suggest the potential involvement of miR-129-5p in the pathological processes of depression. In this proposal, we will investigate the role and mechanism of miR-129-5p in regulation of depression-like behaviours based on neural plasticity and neural circuit by using molecular biology, morphological methods, virus tracing, fiber photometry, chemogenetics, optogenetics, behavioural techniques, and etc. This study may lead to further understand the pathological mechanisms of depression and provide a potential clue for depression diagnosis and therapy.