miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation
作者机构：Department of Integrative Medicine and NeurobiologyState Key Laboratory of Medical NeurobiologySchool of Basic Medical ScienceFudan University200032 ShanghaiChina Institutes of Brain ScienceCollaborative Innovation Center for Brain ScienceFudan University200032 ShanghaiChina Institute of Acupuncture and MoxibustionFudan Institutes of Integrative MedicineFudan University200032 ShanghaiChina Department of AnesthesiologyFudan University Shanghai Cancer Center200032 ShanghaiChina Department of OncologyShanghai Medical CollegeFudan University200032 ShanghaiChina Department of Clinical NeuroscienceCenter for Molecular MedicineKarolinska Institutet17176 StockholmSweden
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2019年第4卷第1期
页 面：434-444页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：This work was sponsored by the National Key R&D Program of China(2017YFB0403803) the National Natural Science Foundation of China(81202746,81871591) the Shanghai Pujiang Program(16PJD014) the Development Project of Shanghai Peak Disciplines-Integrated Chinese and Western Medicine,and China Scholarship Council(201700260280)
主 题：miR surgical therapeutic
摘 要：Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction,also known as postoperative cognitive dysfunction(POCD).miR-124 is one of the most abundant microRNAs in the brain that regulates microglial *** the role of miR-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial *** downstream targets of miR-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation,and vesicle-associated membrane protein 3(VAMP3)was identified as a potential *** kinetics of miR-124/VAMP3 expression was first examined in vitro in microglial cells(primary microglia and BV2 microglial cells)following lipopolysaccharide(LPS)*** induced a time-dependent decrease of miR-124 and upregulated the expression of *** miR-124/VAMP3 expression by using miR-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine *** further examine the role of miR-124/VAMP3 in a surgical setting,we employed a rat surgical trauma *** microglial activation and altered miR-124/VAMP3 expression were observed following surgical *** also altered miR-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous miR-124 and by using electroacupuncture,which is a clinically applicable treatment that modulates microglial function and minimizes postoperative *** determined that electroacupuncture treatment specifically increases the expression of miR-124 in the hypothalamus and *** miR-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation *** s
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