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Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3β pathway in depressed mice

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收录情况： ◇ SCIE

作者：
Zhang Honghan[1] * ; Xie Xin-Hui[1] ; Xu Shu-Xian[1] ; Wang Chao[1] ; Sun Siqi[1] ; Song Xinhua[2] ; Li Ruiling[1] ; Li Ningyuan[1] ; Feng Yuqi[1] ; Duan Hao[1] ; Li Di[3,*1] ; Liu Zhongchun[1,4,*2] ;
单位： [1]Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. [2]Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China. [3]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [4]Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
出处：
DOI： 10.1111/cns.14661
ISSN：

关键词： depression neurogenesis oligodendrocyte-derived exosome sirtuin 2 synaptic plasticity

摘要：
To investigate the antidepressant role of oligodendrocyte-derived exosomes (ODEXs)-containing sirtuin 2 (SIRT2) and the underlying mechanism both in vivo and in vitro.Oligodendrocyte-derived exosomes isolated from mouse serum were administered to mice with chronic unpredictable mild stress (CUMS)-induced depression via the tail vein. The antidepressant effects of ODEXs were assessed through behavioral tests and quantification of alterations in hippocampal neuroplasticity. The role of SIRT2 was confirmed using the selective inhibitor AK-7. Neural stem/progenitor cells (NSPCs) were used to further validate the impact of overexpressed SIRT2 and ODEXs on neurogenesis and synapse formation in vitro.Oligodendrocyte-derived exosome treatment alleviated depressive-like behaviors and restored neurogenesis and synaptic plasticity in CUMS mice. SIRT2 was enriched in ODEXs, and blocking SIRT2 with AK-7 reversed the antidepressant effects of ODEXs. SIRT2 overexpression was sufficient to enhance neurogenesis and synaptic protein expression. Mechanistically, ODEXs mediated transcellular delivery of SIRT2, targeting AKT deacetylation and AKT/GSK-3β signaling to regulate neuroplasticity.This study establishes how ODEXs improve depressive-like behaviors and hippocampal neuroplasticity and might provide a promising therapeutic approach for depression.© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

基金：
National Key Research and Development Program of China, Grant/Award Number: 2018YFC1314600; National Natural Science Foundation of China, Grant/ Award Number: U21A20364
语种：
外文
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 2 区 神经科学 2 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 药学 3 区 神经科学
JCR分区：
出版当年[2022]版：
Q1 NEUROSCIENCES Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 NEUROSCIENCES Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者单位： [1]Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
通讯作者：
通讯机构： [1]Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. [3]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [4]Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. [*1]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [*2]Department of Psychiatry, Renmin Hospital of Wuhan University, No. 99 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.
推荐引用方式(GB/T 7714)：
Zhang Honghan,Xie Xin-Hui,Xu Shu-Xian,et al.Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3β pathway in depressed mice[J].CNS Neuroscience & Therapeutics.2024,30(3):e14661.doi:10.1111/cns.14661.
APA：
Zhang Honghan,Xie Xin-Hui,Xu Shu-Xian,Wang Chao,Sun Siqi...&Liu Zhongchun.(2024).Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3β pathway in depressed mice.CNS Neuroscience & Therapeutics,30,(3)
MLA：
Zhang Honghan,et al."Oligodendrocyte-derived exosomes-containing SIRT2 ameliorates depressive-like behaviors and restores hippocampal neurogenesis and synaptic plasticity via the AKT/GSK-3β pathway in depressed mice".CNS Neuroscience & Therapeutics 30..3(2024):e14661

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