Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury  

作　　者：Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei 

机构地区：[1]Department of Geriatrics,Tianjin Medical University General Hospital,Tianjin,China [2]Tianjin Geriatrics Institute,Tianjin Medical University General Hospital,Tianjin,China [3]Tianjin Neurological Institute,Tianjin Medical University General Hospital,Tianjin,China

出　　处：《Neural Regeneration Research》2024年第9期2010-2018,共9页中国神经再生研究（英文版）

基　　金：supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL);the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG);Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL);Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG);Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006A;Tianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ);China Postdoctoral Science Foundation,No.2022M712392(to ZY).

摘　　要：We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关 键 词：apoptosis C/EBP homologous protein endoplasmic reticulum stress EXOSOME inositol-requiring enzyme 1α MICROGLIA miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1 

分 类 号：R651.15[医药卫生—外科学]