Dong Yu-Xia, Zhang Hui-Yu, Li Hui-Yuan, Liu Pei-Hui, Sui Yi, Sun Xiao-Hong
Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang; Department of Neurology, Fushun Second Hospital, Fushun, Liaoning Province, China.
Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2018 May;13(5):908-914. doi: 10.4103/1673-5374.232486.
The APPSwe/PSEN1dE9 (APP/PS1) transgenic mouse model is an Alzheimer's disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer's disease. Previous clinical autopsy and imaging studies suggest that Alzheimer's disease patients have white matter and oligodendrocyte damage, but the underlying mechanisms of these have not been revealed. Therefore, the present study used APP/PS1 mice to assess cognitive change, myelin loss, and corresponding changes in oligodendrocytes, and to explore the underlying mechanisms. Morris water maze tests were performed to evaluate cognitive change in APP/PS1 mice and normal C57BL/6 mice aged 3 and 6 months. Luxol fast blue staining of the corpus callosum and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for myelin basic protein (MBP) mRNA were carried out to quantify myelin damage. Immunohistochemistry staining for NG2 and qRT-PCR for monocarboxylic acid transporter 1 (MCT1) mRNA were conducted to assess corresponding changes in oligodendrocytes. Our results demonstrate that compared with C57BL/6 mice, there was a downregulation of MBP mRNA in APP/PS1 mice aged 3 months. This became more obvious in APP/PS1 mice aged 6 months accompanied by other abnormalities such as prolonged escape latency in the Morris water maze test, shrinkage of the corpus callosum, upregulation of NG2-immunoreactive cells, and downregulation of MCT1 mRNA. These findings indicate that the involvement of early demyelination at 3 months and the oligodendrocyte dysfunction at 6 months in APP/PS1 mice are in association with Alzheimer's disease pathogenesis.
淀粉样前体蛋白瑞典突变体/早老素1缺失外显子9（APP/PS1）转基因小鼠模型是一种表现出痴呆症状的阿尔茨海默病小鼠模型，常用于探索阿尔茨海默病发展过程中的病理变化。先前的临床尸检和影像学研究表明，阿尔茨海默病患者存在白质和少突胶质细胞损伤，但其潜在机制尚未揭示。因此，本研究使用APP/PS1小鼠评估认知变化、髓鞘丢失以及少突胶质细胞的相应变化，并探索其潜在机制。对3个月和6个月大的APP/PS1小鼠及正常C57BL/6小鼠进行莫里斯水迷宫试验，以评估认知变化。对胼胝体进行卢戈氏碘蓝染色，并对髓鞘碱性蛋白（MBP）mRNA进行定量逆转录-聚合酶链反应（qRT-PCR），以量化髓鞘损伤。进行NG2免疫组化染色和单羧酸转运体1（MCT1）mRNA的qRT-PCR，以评估少突胶质细胞的相应变化。我们的结果表明，与C57BL/6小鼠相比，3个月大的APP/PS1小鼠中MBP mRNA表达下调。这在6个月大的APP/PS1小鼠中更为明显，同时伴有其他异常，如莫里斯水迷宫试验中逃避潜伏期延长、胼胝体萎缩、NG2免疫反应性细胞上调以及MCT1 mRNA下调。这些发现表明，APP/PS1小鼠在3个月时出现早期脱髓鞘以及在6个月时出现少突胶质细胞功能障碍与阿尔茨海默病的发病机制有关。
