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目的:探讨不同月龄APPswe/PS1dE 9双转基因小鼠行为学及病理学的变化特征,为合理运用该模型研究阿尔茨海默病提供可靠依据。方法:采用旷场实验、新物体辨别实验、Y迷宫以及Morris水迷宫等行为学实验方法观察不同月龄的APP/PS1转基因小鼠的运动、新物体辨别以及学习记忆能力的变化;通过免疫组织化学方法检测不同月龄转基因小鼠脑内Aβ含量及星形胶质细胞数量等病理特征的变化。结果:APPswe/PS1dE 9双转基因小鼠的运动能力随月龄增加逐渐下降,9月龄时对新物体的识别、工作记忆及空间学习记忆能力均出现明显损害。同时,该转基因小鼠的海马在6月龄时开始出现Aβ沉积和星形胶质细胞数量增加,9月龄时各种病理变化更为明显。结论:APPswe/PS1dE 9双转基因小鼠在6月龄时开始出现脑内病理改变,9月龄时各种认知行为发生明显异常。提示该转基因小鼠脑内病理改变可能早于行为异常,因此可根据实验目的选取相应月龄的动物。
OBJECTIVE: To investigate the behavioral and pathological features of APPswe / PS1dE 9 double transgenic mice at different months of age in order to provide a reliable basis for the rational use of this model in the study of Alzheimer’s disease. Methods: Behavioral experiments such as open field experiment, new object discrimination experiment, Y-maze and Morris water maze were used to observe the changes of motility, new object discrimination and learning and memory ability of APP / PS1 transgenic mice of different ages. The changes of Aβ and the number of astrocytes in the brain of transgenic mice with different age were detected by chemical methods. Results: The motor ability of APPswe / PS1dE 9 double transgenic mice gradually decreased with the increase of age. At 9 months of age, the recognition of new objects, working memory and spatial learning and memory were significantly impaired. At the same time, the hippocampus of transgenic mice began to show the deposition of Aβ and the number of astrocytes at 6 months of age. All pathological changes were more obvious at 9 months of age. CONCLUSIONS: APPswe / PS1dE 9 double transgenic mice begin pathological changes at 6 months of age, and all cognitive behaviors are significantly abnormal at 9 months of age. Suggesting that the transgenic mouse brain pathological changes may be earlier than the behavioral abnormalities, so according to the purpose of the experiment to select the appropriate age animals.