Mir124介导柴胡疏肝散调控抑郁症肝郁证模型海马神经可塑性的分子机制研究

项目名称： Mir124介导柴胡疏肝散调控抑郁症肝郁证模型海马神经可塑性的分子机制研究

项目编号： No.81503415

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 曹美群

作者单位： 深圳大学

项目金额： 18万元

中文摘要： 抑郁症是最常见的心境障碍，海马神经可塑性障碍是其关键病机，但具体调控机制尚不清楚。研究显示慢性应激经ERK-MAPK通路影响CREB磷酸化导致神经可塑性障碍在抑郁症发病中起着重要作用。申请者前期研究发现Mir124在慢性应激抑郁症肝郁证大鼠海马内明显上调。我们推测慢性应激通过上调mir124表达，经ERK-MAPK通路影响CREB活化,损害海马神经可塑性，是抑郁症肝郁证形成的一个关键机制。为了进一步探索Mir124 调控抑郁症肝郁证海马神经可塑性的具体作用机制。本研究拟选用抑郁症肝郁证大鼠模型，观察海马神经形态和超微结构, 检测海马mir124表达并分析其与ERK-MAPK-CREB通路之间的关联；进一步在细胞水平调控mir124表达，观察其对海马神经元的影响及作用机制；同时以方测证，观察疏肝解郁中药方柴胡疏肝散对此通路的干预作用及机制，以探索抑郁症肝郁证的形成机制及中药抗抑郁的新靶点。

中文关键词： 抑郁症；肝郁证；mir124；ERK-MAPK-CREB；神经可塑性

英文摘要： Depression is a mood disorder most commonly，and hippocampal neuronal plasticity disorder is the key pathogenesis of depression. Numerous studies have shown that chronic stress effects of CREB phosphorylation through ERK-MAPK signaling pathways, further regulation of BDNF gene expression and the neuronal synaptic plasticity, which is one of the important mechanisms of depresion. Our previous studies found that Expression of miR-124 in the hippocampus was significantly increased in chronic stress depresssion rat with liver-Qi stagnation syndrome. Therefore, we hypothesized that chronic stress may modulate the expression of Mir124, and effected the activation of CREB through the ERK-MAPK pathway , further regulated the expression of targwet gene, and cause hippocampal neuronal plasticity impairment, thereby Leading to the formation of depression with liver-Qi stagnation syndrome. In order to further explore the specific mechanism of Mir124 regulation of hippocampal neuronal plasticity of depression with liver-Qi stagnation syndrome. This research plans to select the rat model of depression with liver-qi stagnation syndrome, we will observe the hippocampal neurogenesis, survival, proliferation and synaptic ultrastructure, and test the expression of Mir124 and some Cell factor of ERK-MAPK-CREB signal pathway in hippocampcus, analysis of the correlation between the Mir124 and signal pathway; And we will also study the mechanism of Mir124 effect on the hippocampal neurons at the cellular level . Simultaneous we will observe the effection and mechanism of Prescription Chaihu Shugan on this pathway, in order to explore the mechanism of depression with Liver-qi stagnation syndrome and new target for anti depression medicine.

英文关键词： depression;liver-qi stagnation syndrome;Mir124;ERK-MAPK-CREB;neuron plasticity