NLRP3炎症小体介导的神经炎症在孤独症谱系障碍发病中的机制研究

项目名称： NLRP3炎症小体介导的神经炎症在孤独症谱系障碍发病中的机制研究

项目编号： No.81501180

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： 杜懿杰

作者单位： 复旦大学

项目金额： 17.5万元

中文摘要： 孤独症谱系障碍是一种发生于儿童早期的大脑广泛性发育障碍疾病，临床疗效欠佳源于病因未明。该病的神经免疫炎症假说日益受到学界重视。申请人前期研究发现NLRP3炎症小体作为中枢免疫炎症反应的核心，与中枢免疫效应细胞-小胶质细胞激活密切相关，且发现孤独症大鼠海马NLRP3炎症小体较正常大鼠显著升高，提示海马NLRP3炎症小体介导的神经炎症与孤独症发病密切相关，但其具体的作用机制尚未明确。本研究拟在已建立的孤独症大鼠模型上采用RNA干扰、qPCR、WB、免疫荧光等技术，从体内与体外两个层面，观察孤独症大鼠NLRP3炎症小体对海马小胶质细胞激活的作用机制，阐明其内在调控分子机制和信号通路，并进一步明确NLRP3炎症小体通路对海马神经发育异常的影响和对孤独症相关异常行为的影响，为深入了解孤独症的发病机制拓宽思路，为寻找新型有效的孤独症干预治疗靶点提供科学依据。

中文关键词： 孤独症谱系障碍；神经炎症；NLRP3炎症小体

英文摘要： Autism is a kind of spectrum disorder involved brain pervasive development occurs in early childhood. The exact cause of autism is unknown. At present, the neural immune hypothesis of autism is regarded more and more important. Our previous research found that the NLRP3 inflammasome can cause immune inflammation. NLRP3 inflammasome is closely related to the microglia which is central immune effector cells. We also found that the NLRP3 in hippocampus of autism rats increased significantly than normal rats. Our study suggest that the hippocampus NLRP3 mediated inflammation and the pathogenesis of nerve mechanisms associated with autism, but its specific pathogeny remain unknown. This study intends to adopt RNA interference, microRNA, WB, immunofluorescence technique in the rat model of autism (in vivo and in vitro), observe the mechanism of NLRP3 inflammasome and demonstrate how can activate the microglia, explain the internal control mechanism and modulatory effects on hippocampal neuronal development. And then demonstrate the effects of NLRP3 inflammasome on autism related abnormal behaviors. We hope our study could provide the scientific basis for pathogenesis cause of autism.

英文关键词： Autism spectrum disorder;Neuro-inflammation;NLRP3 inflammasome