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Mossy cell synaptic dysfunction causes memory imprecision via miR-128 inhibition of STIM2 in Alzheimer's disease mouse model

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单位: [1]Huazhong Univ Sci & Technol, Dept Physiol, Sch Basic Med, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430030, Peoples R China [3]Huazhong Univ Sci & Technol, Wuhan Ctr Brain Sci, Inst Brain Res, Wuhan, Peoples R China [4]Huazhong Univ Sci & Technol,Dept Orthopaed,Tongji Hosp,Tongji Med Coll,Wuhan,Peoples R China [5]Huazhong Univ Sci & Technol, Dept Neurobiol, Sch Basic Med, Wuhan, Peoples R China
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关键词: Alzheimer's disease memory imprecision MiR-128 mossy cell synaptic dysfunction

摘要:
Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in a mouse model of early Alzheimer's disease (AD). Single-cell RNA sequencing reveals that miR-128 that binds to a 3 ' UTR of STIM2 and inhibits STIM2 translation is increasingly expressed in MCs from AD mice. Silencing miR-128 or disrupting miR-128 binding to STIM2 evokes STIM2 expression, restores synaptic function, and rescues memory imprecision in AD mice. Comparable findings are achieved by directly engineering MCs with the expression of STIM2. This study unveils a key synaptic and molecular mechanism that dictates how memory maintains or losses its details and warrants a promising target for therapeutic intervention of memory decays in the early stage of AD.

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出版当年[2019]版:
大类 | 1 区 生物
小类 | 1 区 老年医学 2 区 细胞生物学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 老年医学 2 区 细胞生物学
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出版当年[2018]版:
Q1 CELL BIOLOGY Q1 GERIATRICS & GERONTOLOGY
最新[2023]版:
Q1 CELL BIOLOGY Q1 GERIATRICS & GERONTOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者单位: [1]Huazhong Univ Sci & Technol, Dept Physiol, Sch Basic Med, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430030, Peoples R China [3]Huazhong Univ Sci & Technol, Wuhan Ctr Brain Sci, Inst Brain Res, Wuhan, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol, Dept Physiol, Sch Basic Med, Wuhan 430030, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Wuhan 430030, Peoples R China [3]Huazhong Univ Sci & Technol, Wuhan Ctr Brain Sci, Inst Brain Res, Wuhan, Peoples R China [5]Huazhong Univ Sci & Technol, Dept Neurobiol, Sch Basic Med, Wuhan, Peoples R China
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