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首页> 外文期刊>Neuron >Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease
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Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease

机译:增强髓鞘更新逆转阿尔茨海默病的鼠模型中的认知功能障碍

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摘要

Severe cognitive decline is a hallmark of Alzheimer's disease (AD). In addition to gray matter loss, significant white matter pathology has been identified in AD patients. Here, we characterized the dynamics of myelin generation and loss in the APP/PS1 mouse model of AD. Unexpectedly, we observed a dramatic increase in the rate of new myelin formation in APP/PS1 mice, reminiscent of the robust oligodendroglial response to demyelination. Despite this increase, overall levels of myelination are decreased in the cortex and hippo campus of APP/PS1 mice and postmortem AD tissue. Genetically or pharmacologically enhancing myelin renewal, by oligodendroglial deletion of the muscarinic M1 receptor or systemic administration of the promyelinating drug clemastine, improved the performance of APP/PS1 mice in memory-related tasks and increased hippocampal sharp wave ripples. Taken together, these results demonstrate the potential of enhancing myelination as a therapeutic strategy to alleviate AD-related cognitive impairment.
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著录项

  • 来源
    《Neuron》 |2021年第14期|共22页
  • 作者单位

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Third Mil Med Univ Chongqing Key Lab Neurobiol Brain &

    Intelligence Res Key Lab Chongqing Educ C;

    Third Mil Med Univ Chongqing Key Lab Neurobiol Brain &

    Intelligence Res Key Lab Chongqing Educ C;

    Univ Calif San Francisco Dept Neurol UCSF Weill Inst Neurosci San Francisco CA 94158 USA;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

    Univ Calif San Francisco Dept Neurol UCSF Weill Inst Neurosci San Francisco CA 94158 USA;

    Third Mil Med Univ Dept Histol &

    Embryol Brain &

    Intelligence Res Key Lab Chongqing Educ Commiss;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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