miRNA-134介导的突触可塑性调节在抑郁症发病中的作用及机制研究

脑功能失调是抑郁症发病的首要生物学因素，其中突触可塑性调节是导致脑功能失调的关键机制。申请者首次报导了慢性应激刺激诱导的抑郁症大鼠杏仁核神经元发生了突触可塑性变化。最近，我们预实验结果又发现抑郁症大鼠杏仁核miR-134显著过表达，而下调miR-134的表达可有效改善抑郁症状的发生。miR-134是新发现的一个潜在的突触可塑性调节因子，但miR-134在抑郁症发病中的作用尚无报导。因此本课题拟在前期工作基础上，重点研究以下内容：（1）在细胞和分子水平研究miR-134对突触可塑性的调控机制，及其对杏仁核神经元网络结构、功能的影响；（2）在整体水平建立慢性应激刺激诱导的抑郁症大鼠模型，探讨体内miR-134对突触可塑性介导的抑郁症脑功能失调乃至行为改变的影响。从而阐明miR-134调控抑郁症突触可塑性的分子信号机制，为干预抑郁症的发生发展提供理论依据和药物治疗新靶点。

Brain dysfunction is the primary factor leading to depression while synaptic plasticity is the key mechanism to initiate the brain dysfunction. We first investigated and reported the important role of synaptic plasticity in the amygdala in chronic unpredicted mild stress induced depression animal model. miR-134 is a newly identified potential factor related to synaptic plasticity.Hower, the role of miR-134 in depression has not been reported. Recently, we found the level of miR-134 is increased in the amygdala and involed in the neuronal synaptic plasticity in chronic variable stressed rats while neuroprotective agent curcumin could inhibited the overexpression of miR-134 and up-regulated the expression of synaptic plasticity-related proteins,and thus improved the depressive disorders dramatically.Therefore, based on the previous findings, we will further investigated the following aspects:(1)investigate the role of miR-134 on the function of amygdala neuronal circuit and the mechanism of miR-134 on regulatingthe synaptic plasticity; (2) illustrate the mechanisms by which miR-134 signaling pathway could contribute to the synaptic plasticity in vivo and as well as depressive disorders in chronic stress induced depressive rats. Controlling the expression of this pathway could improve mental disorders therapy and provide the new target for drug discovery and development.