老年雄性APP/PS1模型小鼠大脑海马齿状回内有髓神经纤维结构的体视学研究

Stereological study of the structure of the myelinated nerve fibers in the dentate gyrus of the aged APP/PS1 transgenetic mice

目的:运用现代体视学方法定量研究16月龄雄性APP/PS1双转基因小鼠海马齿状回有髓神经纤维的结构改变,以期深入了解阿尔茨海默病海马的形态学改变。方法:Morris水迷宫方法测试16月龄雄性野生型小鼠和16月龄雄性APP/PS1双转基因模型小鼠的空间学习记忆能力,透射电子显微镜技术和现代体视学方法定量研究模型小鼠和野生型小鼠海马齿状回内有髓神经纤维长度、有髓神经纤维及其轴突和髓鞘体积等参数。结果:Morris水迷宫结果显示在前六天的隐蔽站台试验中模型组小鼠逃避潜伏期明显长于野生型小鼠(分组效应:F=9.952,P=0.008;时间效应:F=3.082,P=0.023;时间分组交互作用:F=0.312,P=0.873),在第七天的空间探索试验中模型小鼠穿台次数明显少于野生型小鼠(F=2.961,P=0.011),原平台所在象限停留时间百分比明显小于野生型小鼠(F=0.090,P=0.002)。虽然两组小鼠海马体积没有统计学差异,但是DG区内有髓神经纤维的超微结构均存在退行性改变,体视学定量分析结果显示在0.7~1.2μm直径段模型组小鼠海马DG内有髓神经纤维长度较野生型组明显降低(P=0.022)。结论:16月龄时APP/PS1模型小鼠空间学习记忆能力明显减退,且海马DG内0.7~1.2μm直径段有髓神经纤维明显丢失可能是APP/PS1模型小鼠空间学习记忆能力进行性减退的结构基础之一。

Objective：To investigate the changes of the myelinated nerve fibers in the dent-ate gyrus（DG）of the 16-month-old male APP/PS1 transgenetic model mice using the unbiased s-tereological methods in order to further understand the morphological changes in the hippoca-mpus of the Alzheimer＇s disease. Methods：The spatial learning and memory abilities of the 16month-old male APP/PS1 model and wild-type mice were investigated using the Morris Water Maze test. The total length of the myelinated fibers,the total volumes of the myelinated fibers,the axons of the myelinated fibers and the myelin sheaths of the myelinated fibers,the inner diameter and outer diameter of the myelinated fibers in the DG of the mice in two groups were investigated by the transmission electron microscope and the unbiased stereological methods. Results：Morris Water Maze results showed that the escape latency of the model mice was signi-ficantly higher than that of the wild-type mice（group effect：F=9.952,P=0.008;time effect：F=3.082,P=0.023;time group interaction：F=0.312,P=0.873）. The target zone frequency in the probe trial task of the model mice was significantly decreased compared with that of the wild-type（F=2.961,P=0.011）,so was the percentage of time in target quadrant zone（F=0.090,P=0.002）. The hippocampal volume and the dentate gyrus volume were not significantly different between the model mice and the wild-type mice. However,the myelin sheaths of the myelinated fibers in the DG of both group mice existed degenerative changes.Moreover,the stereological results showed that the total length of the myelinated fibers with the diameter range from 0.7 to 1.2μm in the DG of the model mice was significantly decreased when compared with that of wild-type mice（P=0.022）. Conclusion：The spatial learning and memory abilities of the 16-month-old male APP/PS1 model mice were decreased significantly. The significant loss of myelinated fibers with the diameter range from 0.7 to1.2 μm in the DG of the APP/PS1 model mice might be one of the structural bases for the memory and learning deficits of the old APP/PS1 model mice.