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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 quantitatively study the structural changes of dentate gyrus myelinated nerve fibers in 16-month-old male APP / PS1 double transgenic mice in order to gain a deeper understanding of the morphological changes in the hippocampus of Alzheimer’s disease. METHODS: The spatial learning and memory abilities of 16-month-old male and 16-month-old male APP / PS1 double transgenic mice were tested by Morris water maze method. Transmission electron microscopy and modern stereological methods were used to quantitatively study the effects of The length of myelinated nerve fibers, the myelinated nerve fibers, axon and myelin volume in hippocampal dentate gyms of wild-type mice and other parameters. Results: Morris water maze results showed that in the first six days of hidden platform test, the escape latency of model mice was significantly longer than that of wild-type mice (grouping effect: F = 9.952, P = 0.008; time effect: F = 3.082, P = 0.023 (F = 0.312, P = 0.873). In the seventh day of space exploration experiment, the number of wearing mice in model mice was significantly less than that in wild type mice (F = 2.961, P = 0.011) The quadrant retention time was significantly less than that of wild-type mice (F = 0.090, P = 0.002). Although there was no significant difference in hippocampal volume between the two groups, the ultrastructure of myelinated nerve fibers in DG area were degenerated. Stereopsis quantitative analysis showed that in hippocampal DG of 0.7 ~ 1.2μm diameter model group The length of myelinated nerve fibers was significantly lower than that of the wild-type group (P = 0.022). CONCLUSION: The spatial learning and memory abilities of APP / PS1 mice significantly decreased at 16 months of age. The significant loss of myelinated fibers in 0.7 ~ 1.2 μm diameter DG in hippocampus DG may be a result of the progressive decline of spatial learning and memory in APP / PS1 mice One of the structural foundations.