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Direct Current Electric Field Coordinates the Migration of BV2 Microglia via ERK/GSK3β/Cofilin Signaling Pathway

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单位: [1]Shanghai Jiao Tong Univ, Renji Hosp, Brain Injury Ctr, Sch Med, 160 Pujian Rd, Shanghai 200127, Peoples R China [2]Shanghai Inst Head Trauma, Shanghai 200127, Peoples R China [3]Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA [4]Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China [5]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Neurosurg,Wuhan 430030,Peoples R China [6]Tsinghua Univ, Yuquan Hosp, Sch Clin Med, Dept Neurosurg, Beijing 100040, Peoples R China
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关键词: Direct current electric field Microglia Electrotaxis Cell migration ERK/GSK3 beta/cofilin axis

摘要:
Direct current electric field (DCEF) steers the migration of various neural cells. Microglia, as macrophage of the central nervous system (CNS), however, have not been reported to engage in electrotaxis. Here, we applied electric fields to an in vitro environment and found directional migration of BV2 microglia toward the cathode, in a DCEF strength-dependent manner. Transcriptome analysis then revealed significant changes in the mitogen-activated protein kinase cascades. In terms of mechanism, DCEF coordinated microglia movement by regulating the ERK/GSK3 beta/cofilin signaling pathway, and PMA (protein kinase C activator) reversed cell migration through intervention of the ERK/GSK3 beta/cofilin axis. Meanwhile, LiCl (GSK3 beta inhibitor) showed similar functions to PMA in the electrotaxis of microglia. Furthermore, pharmacological and genetic suppression of GSK3 beta or cofilin also modulated microglia directional migration under DCEF. Collectively, we discovered the electrotaxis of BV2 microglia and the essential role of the ERK/GSK3 beta/cofilin axis in regulating cell migration via modulation of F-actin redistribution. This research highlights new insight toward mediating BV2 directional migration and provides potential direction for novel therapeutic strategies of CNS diseases.

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出版当年[2021]版:
大类 | 2 区 医学
小类 | 2 区 神经科学
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大类 | 2 区 医学
小类 | 2 区 神经科学
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Q1 NEUROSCIENCES
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Q1 NEUROSCIENCES

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第一作者单位: [1]Shanghai Jiao Tong Univ, Renji Hosp, Brain Injury Ctr, Sch Med, 160 Pujian Rd, Shanghai 200127, Peoples R China [2]Shanghai Inst Head Trauma, Shanghai 200127, Peoples R China
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通讯机构: [1]Shanghai Jiao Tong Univ, Renji Hosp, Brain Injury Ctr, Sch Med, 160 Pujian Rd, Shanghai 200127, Peoples R China [2]Shanghai Inst Head Trauma, Shanghai 200127, Peoples R China
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