中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 908-914.doi: 10.4103/1673-5374.232486

• 原著:退行性病与再生 • 上一篇    下一篇

阿尔茨海默病发病与早期脱髓鞘和少突胶质细胞的功能障碍有关？

  

  • 收稿日期:2018-01-09 出版日期:2018-05-15 发布日期:2018-05-15
  • 基金资助:

    2015年辽宁科技优惠基金(2015年)、辽宁省自然科学基金(20170541021)、沈阳科技项目(F16-206-9-12)、国家自然科学基金(81371395)、辽宁省自然科学基金(2015020547)、中国博士后科学基金(2015M581375)

Association between Alzheimer’s disease pathogenesis and early demyelination and oligodendrocyte dysfunction

 Yu-Xia Dong1, 2, Hui-Yu Zhang1, Hui-Yuan Li1, Pei-Hui Liu1, 3, Yi Sui1, 4, Xiao-Hong Sun1   

  1. 1 Department of Neurology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China;
    2 Department of Neurology, Fushun Second Hospital, Fushun, Liaoning Province, China;
    3 Department of Neurology, Huludao Central Hospital, Huludao, Liaoning Province, China;
    4 Department of Neurology, Shenyang First People’s Hospital, Shenyang, Liaoning Province, China
  • Received:2018-01-09 Online:2018-05-15 Published:2018-05-15
  • Contact: Xiao-Hong Sun, Ph.D.,sunxiaohong1972@hotmail.com
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81371395; the Liaoning Scientific and Technological Preferential Finance for Returned Overseas 2015 of China, No. [2015]125; the Natural Science Foundation of Liaoning Province of China, No. 20170541021, 2015020547; a grant from the Shenyang Science Technology Project, No. F16-206-9-12; and the China Post-doctoral Science Foundation, No. 2015M581375.

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摘要：

APP/PS1转基因小鼠模型为成熟的阿尔茨海默病小鼠模型，可出现痴呆症状，目前众多实验应用APP/PS1转基因小鼠模型探讨阿尔茨海默病发生发展过程中的病理改变。以往临床尸检及影像学研究提示阿尔茨海默病患者存在白质和少突胶质细胞损伤，但有关白质和少突胶质细胞损伤的潜在机制揭示的很少。为此，作者在观察APP/PS1转基因小鼠髓鞘脱失和少突胶质细胞的相应病理改变时探讨可能机制。作者采用Morris水迷测试评价3，6月龄APP/PS1转基因小鼠和C57BL/6小鼠认知功能改变，用髓鞘染色方法行胼胝体染色及髓鞘碱性蛋白mRNA实时荧光定量PCR测定髓鞘脱失程度，硫酸软骨素蛋白多糖免疫组织化学染色和单羧酸转运蛋白1 mRNA实时荧光定量PCR测定少突胶质细胞的变化。发现与C57BL/6小鼠相比，APP/PS1转基因小鼠3月龄时颞叶髓鞘磷脂碱性蛋白mRNA表达量明显下降，6月龄时颞叶髓鞘磷脂碱性蛋白 mRNA表达量进一步下降，Morris水迷宫逃避潜伏期延长、胼胝体萎缩、颞叶硫酸软骨素蛋白多糖阳性细胞增多、单羧酸转运蛋白1 mRNA表达量明显下降。上述数据显示，APP/PS1转基因小鼠3月龄时出现早期脱髓鞘改变，6月龄时出现少突胶质细胞功能异常，可导致阿尔茨海默病的发病。

orcid:0000-0002-8937-6228(Xiao-Hong Sun)

关键词: 阿尔茨海默病, APP/PS1转基因小鼠, Morris水迷宫, 胼胝体, 脱髓鞘, 少突胶质细胞, 髓鞘碱性蛋白, 单羧酸转移酶1, 髓鞘染色, 硫酸软骨素蛋白多糖, 神经再生, 神经退行性变

Abstract:

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.

Key words: nerve regeneration, Alzheimer’s disease, APP/PS1 mice, Morris water maze test, corpus callosum, demyelination, oligodendrocytes, myelin basic protein, monocarboxylic acid transporter 1, neural regeneration