项目名称: PSD93在APP/PS1小鼠突触可塑性中的病理作用及其机制
项目编号: No.81471102
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 赵辉
作者单位: 南京大学
项目金额: 70万元
中文摘要: 突触损害与Alzheimer's disease(AD)的学习记忆障碍密切相关。前期研究发现,APP/PS1小鼠与B6小鼠相比,PSD93表达明显升高。PSD93RNA干扰处理APP/PS1小鼠后,学习和记忆功能改善,同时部分突触蛋白表达水平提高。提示PSD93与 AD的学习记忆障碍相关。本课题利用行为学、病理学、分子生物学等技术进行以下体内外研究:1)PSD93与认知障碍的相关性以及在损伤AD突触可塑性中的病理作用;2)PSD93是否通过SynGAP通路调节AD的突触可塑性。本研究首次将PSD93与APP/PS1小鼠的突触可塑性病理性损害相联系,阐明AD突触可塑性病理性损伤的分子调控机制,为临床早期诊断和治疗提供新的靶点。
中文关键词: 阿尔茨海默病;突触可塑性;PSD93
英文摘要: The synaptic damage is closely related to the impairment of learning and memory of Alzheimer's disease. Preliminary study demonstrated that compared with B6 mice, the expression of PSD93 in APP/PS1 double transgenic mice was significantly increased. after managed with short interfering RNA of PSD93, the learning and memory function of APP/PS1 double transgenic mice was improved, meanwhile the levels of some synapse proteins was also enhanced,suggesting PSD93 was related with the impairment of learning and memory of Alzheimer's disease. This research use behavior, pathology, molecular biology techniques as following in vitro and in vivo: 1) to demonstrate the correlation between PSD93 and cognitive impairment and PSD93 is a key pathological role in the pathogenesis of AD. 2) to identify whether PSD93 regulated the synaptic plasticity remodeling by the SynGAP passway. This study is the first to demonstrate the relationship between PSD93 and the synaptic plasticity pathological damage of APP/PS1 mice, In addition, this study will investigate the molecular mechanisms of synaptic plasticity pathological damage of AD, provide new targets for early clinical diagnosis and treatment for AD.
英文关键词: Alzheimer’s disease;the synaptic plasticity;PSD93