POMGnT1基因突变小鼠海马神经元异常迁移机制的的实验研究

项目名称： POMGnT1基因突变小鼠海马神经元异常迁移机制的的实验研究

项目编号： No.30800346

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 李小凤

作者单位： 重庆医科大学

项目金额： 19万元

中文摘要： 前期工作发现，POMGnT1基因突变小鼠的大脑和小脑出现形态结构异常，机制分别为发育期神经元的迁移过度和迁移不足；同时发现海马的形态结构也出现异常。本课题拟用Morris水迷宫试验评定突变体成年小鼠的记忆认知行为；生物电记录技术测定LTP，观察突变体小鼠海马的电生理变化；光镜、电镜观察海马的显微和超微结构的变化；免疫荧光染色显示不同发育阶段海马的神经细胞、胶质细胞、基膜和胶质界膜的定位/变化；通过Br-dU标记和计数试验，了解海马内新生神经元的迁移过程；最后通过基因芯片技术分析海马cDNA的差异表达来了解与迁移有关的基因表达变化，试图阐释POMGnT1基因突变小鼠海马神经元异常迁移的分子生物学机制。 该课题将为海马神经元的迁移机理研究提供更多的线索，为将来成功的神经干细胞海马移植定位提供指导意义。

中文关键词： POMGnT1基因突变；海马；发病机制；神经元迁移；肌-眼-脑病

英文摘要： In preliminary experiment,cerebra and cerebella of POMGnT1 mutant mice were found morphologically abnormal and the underlying mechanism were neuronal overmigration and undermigration in developmental stages,respectively ;meanwhile,hippocampi were found abnormal as well .In this project, biological mechanism underlying abnormal neuronal migration in hippocampi of POMGnT1 mutant mice is investigated :Morris water-maze to evaluate behavior of memory and recognition in adult mice ; bio- electrical recording to measure LTP and observe electrical physiological change of hippocampi ;light microscope and electronic microscope to observe micro and ultra-micro changes ;immunofluorescence staining to show the changes of neurons ，glia ，base membrane and glia limitant in different developmental stages ; Br-dU labelling and counting test to know the process of neuronal migration ; microarray to analyze cDNA differential expression and understand the changes of relevant gene expression . This project will provide more clues for research of mechanism underlying neuronal migration of hippocampi and help neural stem cells implantation successfully position in hipocampus .

英文关键词： POMGnT1 gene mutant ; hippocampus; mechannism ; neuronal migration; Muscle-Eye-Brain disease