早期APP/PS1转基因阿尔茨海默病小鼠海马结构内有髓神经纤维改变的体视学研究

目的 探讨早期APP/PS1转基因阿尔茨海默病(Alzheimer's disease,AD)小鼠海马结构内有髓神经纤维及髓鞘的改变.方法 运用Morris水迷宫方法测试10月龄APP/PS1转基因AD小鼠和同月龄野生型小鼠的空间学习和记忆能力改变的情况;运用无偏体视学方法结合透射电子显微镜技术对各组小鼠海马结构总体积,CA1和齿状回(dentate gyrus,DG)内有髓神经纤维的总长度和总体积,以及有髓神经纤维髓鞘总体积进行三维定量研究.结果 ①与野生型小鼠相比,10月龄APP/PS1转基因AD小鼠的逃避潜伏期显著性增加(P＜0.05),所在象限游泳时间百分比显著减少(P＜0.01),而穿台次数差异无统计学意义(P＞0.05);②与野生型小鼠相比,10月龄APP/PS1转基因AD小鼠海马体积、CA1体积、DG体积均显著性减小(P ＜0.05,P＜0.01);③与同月龄野生型小鼠相比,10月龄APP/PS1转基因AD小鼠海马CA1区和DG内有髓神经纤维的总长度差异没有统计学意义(P＞0.05),但是海马CA1区和DG内有髓神经纤维的总体积显著性减小(P＜0.05),髓鞘总体积也显著减小(P ＜0.05,P＜0.01).结论 10月龄时APP/PS1转基因AD小鼠海马CA1和DG内均存在脱髓鞘改变,可能是引起AD早期空间学习记忆能力减退的结构基础之一.

Changes of myelinated nerve fibers in hippocampus of APP/PS1 transgenic mice with early symptoms of Alzheimer's disease: a stereological study

Objective To investigate the changes of myelinated fibers and myelin sheaths in the hippocampus of APP/PS1 transgenetic mice with early onset of symptoms of Alzheimer's Disease (AD).Methods The spatial learaning and memory abilities of 10-month-old APP/PS1 transgenic mice and wild-type mice were evaluated with Morris water maze test.The volume of the hippocampus,CA1 and the dentate gyrus (DG),and the length of the myelinated nerve fibers and the total volume of the myelinated nerve fibers and myelin sheathes in the CA1 region and the DG were determined using an unbiased stereological method coupled with electron microscope technique.Results Compared with the wild-type mice,the transgenic mice showed a significantly increased mean escape latency (P ＜ 0.05) and a decreased percentage of time staying in the target quadrant (P ＜ 0.01),but with comparable frequencies of crossing the platform location (P ＞0.05).The volumes of the hippocampus,CA1 region and the DG were significantly decreased in the transgenic mice compared with those in the wild-type mice (P ＜ 0.01,P ＜ 0.05).The total length of the myelinated fibers in the hippocampal CA1 region and DG did not differ significantly between the transgenic and wild-type mice (P ＞ 0.05),but the total volumes of the myelinated fibers and myelin sheathes in the hippocampal CA1 region and DG were significantly smaller in the transgenic mice (P ＜ 0.05,P ＜ 0.01).Conclusion Demyelization occurs in the hippocampal CA1 region and DG of 10-month-old APP/PS1 transgenic mice that show early AD symptoms,and these changes might contribute as one of the structural basis to memory and learning deficits in the mice.