首页 文献索引 SCI期刊 AI助手
首页 正文

Neurobiology of disease. 2020 Feb:134:104617. doi: 10.1016/j.nbd.2019.104617 Q15.12024

Environmental enrichment prevents Aβ oligomer-induced synaptic dysfunction through mirna-132 and hdac3 signaling pathways

环境丰富通过miRNA-132和HDAC3信号通路防止Aβ寡聚体诱导的突触功能障碍 翻译改进

Zhiyun Wei  1, Xingjun Meng  2, Rachid El Fatimy  3, Bowen Sun  3, Dongmei Mai  2, Junfang Zhang  4, Ramil Arora  3, Ailiang Zeng  3, Pingyi Xu  5, Shaogang Qu  2, Anna M Krichevsky  3, Dennis J Selkoe  3, Shaomin Li  6

作者单位 +展开

作者单位

  • 1 Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, United States of America; Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
  • 2 Central Laboratory and Department of Neurology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan 528300, Guangdong, China.
  • 3 Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, United States of America.
  • 4 Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, United States of America; Department of Physiology and Pharmacology, School of Medicine, Ningbo University, Ningbo, HMS Initiative for RNA Medicine, Zhejiang, China.
  • 5 Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 6 Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, United States of America. Electronic address: sli11@bwh.harvard.edu.

    • DOI: 10.1016/j.nbd.2019.104617 PMID: 31669733

    摘要 Ai翻译

    As the most common cause of progressive cognitive decline in humans, Alzheimer's disease (AD) has been intensively studied, but the mechanisms underlying its profound synaptic dysfunction remain unclear. Here we confirm that exposing wild-type mice to an enriched environment (EE) facilitates signaling in the hippocampus that promotes long-term potentiation (LTP). Exposing the hippocampus of mice kept in standard housing to soluble Aβ oligomers impairs LTP, but EE can fully prevent this. Mechanistically, the key molecular features of the EE benefit are an upregulation of miRNA-132 and an inhibition of histone deacetylase (HDAC) signaling. Specifically, soluble Aβ oligomers decreased miR-132 expression and increased HDAC3 levels in cultured primary neurons. Further, we provide evidence that HDAC3 is a direct target of miR-132. Overexpressing miR-132 or injecting an HDAC3 inhibitor into mice in standard housing mimics the benefits of EE in enhancing hippocampal LTP and preventing hippocampal impairment by Aβ oligomers in vivo. We conclude that EE enhances hippocampal synaptic plasticity by upregulating miRNA-132 and reducing HDAC3 signaling in a way that counteracts the synaptotoxicity of human Aβ oligomers. Our findings provide a rationale for prolonged exposure to cognitive novelty and/or epigenetic modulation to lessen the progressive effects of Aβ accumulation during human brain aging.

    Keywords：environmental enrichment; aβ oligomers; synaptic dysfunction; hdac3

    关键词：环境丰富刺激; 淀粉样蛋白寡聚体; 突触功能障碍; hdac3

    Copyright © Neurobiology of disease. 中文内容为AI机器翻译，仅供参考！

    相关内容

    期刊名：Neurobiology of disease

    缩写：NEUROBIOL DIS

    ISSN：0969-9961

    e-ISSN：1095-953X

    IF/分区：5.1/Q1

    文章目录 更多期刊信息

    全文链接
    官方链接
    PMC全文
    引文链接
    复制
    已复制！
    推荐内容
    Environmental enrichment prevents Aβ oligomer-induced synaptic dysfunction through mirna-132 and hdac3 signaling pathways