AD小鼠成年海马神经发生异常对空间参考记忆编码的影响及其机制研究

项目名称： AD小鼠成年海马神经发生异常对空间参考记忆编码的影响及其机制研究

项目编号： No.31671106

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 神经、认识与心理学

项目作者： 朱志茹

作者单位： 中国人民解放军第三军医大学

项目金额： 25万元

中文摘要： β淀粉样蛋白（Aβ）斑块在脑内沉积之前，AD患者即已出现早期认知功能下降，特别是空间参考记忆的障碍。而空间参考记忆的形成依赖于海马齿状回成年期新生颗粒神经元(Young adult-born granule cells，YGCs)对空间信息的编码。我们前期研究发现，AD早期异常增多的可溶性Aβ可通过多种分子机制造成DG中YGCs形态结构异常。然而，这些细胞水平的异常如何引发空间信息编码异常，进而损伤空间参考记忆，目前尚不清楚。本项目拟以AD转基因小鼠齿状回YGCs为研究对象，采用分子生物学、形态学及电生理技术，研究AD早期YGCs结构和功能改变。研究结果为理解AD早期认知功能损伤的机制提供理论基础，为AD的早期诊断治疗提供新的思路。

中文关键词： 海马齿状回；神经发生；空间参考记忆；神经信息编码；阿尔茨海默病

英文摘要： AD patients show cognitive decline, especially spatial reference memory impairment, in early phase of AD without amyloid deposition. Young adult-born granule cells (YGCs) in hippocampal dentate gyrus (DG) mediate pattern separation of spatial information which forming the basis for the formation of spatial reference memory. Our previous studies have revealed that elevated Aβ induced structural and functional alternation in the granule cells through various molecular mechanisms. However, it is not known how these cellular changes will in turn alter pattern separation and further cause spatial reference memory impairment. Our present project will focus on the abnormal alternation of YGCs from APPswe/PS1dE mice. Using molecular biological, morphological and electrophysiological techniques, we will investigate structural and functional alternation in YGCs from APPswe/PS1dE mice. The knowledge gained from this study will not only shed novel insights into the neuronal mechanisms of cognitive defects in early AD, but will also develop insights into therapeutic strategies to prevent or treat AD.

英文关键词： Hippocampal dentate gyrus;Neurogenesis;Spatial reference memory;Neural information coding;Alzhemer's disease