类朊蛋白"Sho"调控抑郁作用的研究

项目名称： 类朊蛋白"Sho"调控抑郁作用的研究

项目编号： No.31201714

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 孟轲音

作者单位： 中国人民解放军军事医学科学院

项目金额： 23万元

中文摘要： 近几年新发现的类朊蛋白-Sho，可能是朊病毒致病的一个重要协助因子，它给朊病毒病发病机理研究带来新的希望，迫切需要人们对Sho开展相关研究。课题组前期通过已建立的Sho高表达和基因敲除两种小鼠模型进行强迫游泳、悬尾等抑郁性行为学研究发现，Sho具有调控抑郁的作用。本项目拟继续以Sho两种模型小鼠为基础，进一步分析Sho高表达和缺失对小鼠海马神经元再生、海马结构、海马神经元形态等的影响，同时，结合LC-MS/MS等蛋白质组学技术及生物信息学知识，分析Sho调控抑郁作用的分子机制。本项目的研究将为理解朊病毒病发病机理及朊病毒病患者抑郁的临床症状提供新的理论依据，同时，也为人类抑郁症治疗提供一个新的潜在药物靶标。

中文关键词： 抑郁症；Shadoo蛋白缺失；神经元损伤；神经递质；

英文摘要： Sho, a paralogue of prion protein discovered in recent years, is probably an important co-factor in prion disease pathogenesis. Further study for the Sho protein will give us a new hope to understand the mechanism of prion pathogenesis. In our preliminary study, two mouse models, the Sho gene overexpression or knock out models, were undergone depression behaviour tests such as force swimming test (FST) and tail suspension test. These studies suggested that Sho may have an effect on the regulation of depression. In this proposal study, we will further analyse the hippocampus neuronal regeneration, the structure of hippocampus, and the morphology of hippocampus neurons in mouse models of both Sho gene overexpression and Sho gene knock out. Meanwhile, by using LC-MS/MS, proteomics techniques and knowledge based bioinfomatics methods, we will study and analyse the effect of Sho on the mechanism of molecular regulation of depression. This study will provide the foundation of understanding the mechanism of prion pathogenesis, and the explanation of why patients with prion disease show depression syndrome. Furthermore, this study will also provide a new drug target for the treatment of human depression syndrome.

英文关键词： Depressive disorder；deficiency of Shadoo protein；neuron damage；neurotransmitter；