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Direct Current Electric Field Coordinates the Migration of BV2 Microglia via ERK/GSK3β/Cofilin Signaling Pathway
Yuxiao Ma1,2, Chun Yang1,2, Qian Liang3
1Brain Injury Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, People's Republic of China.
Abstract:
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/GSK3β/cofilin signaling pathway, and PMA (protein kinase C activator) reversed cell migration through intervention of the ERK/GSK3β/cofilin axis. Meanwhile, LiCl (GSK3β inhibitor) showed similar functions to PMA in the electrotaxis of microglia. Furthermore, pharmacological and genetic suppression of GSK3β or cofilin also modulated microglia directional migration under DCEF. Collectively, we discovered the electrotaxis of BV2 microglia and the essential role of the ERK/GSK3β/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.
Insights
This study reveals that direct current electric fields (DCEF) induce directional migration in BV2 microglia, a key immune cell in the central nervous system (CNS). This electrotaxis is regulated by the ERK/GSK3β/cofilin signaling pathway, offering new therapeutic avenues for CNS diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Direct current electric fields (DCEF) are known to influence neural cell migration.
- Microglia, the resident macrophages of the central nervous system (CNS), have not been previously studied for their response to electric fields (electrotaxis).
Purpose of the Study:
- To investigate whether BV2 microglia exhibit electrotaxis under DCEF.
- To elucidate the underlying molecular mechanisms governing microglia migration in response to electric fields.
Main Methods:
- Application of DCEF to in vitro BV2 microglia cultures.
- Transcriptome analysis to identify affected signaling pathways.
- Pharmacological and genetic manipulation of key signaling molecules (ERK, GSK3β, cofilin).
Main Results:
- BV2 microglia demonstrated directional migration towards the cathode in a DCEF strength-dependent manner.
- Transcriptome analysis revealed significant alterations in mitogen-activated protein kinase cascades.
- The ERK/GSK3β/cofilin signaling pathway was identified as crucial for DCEF-mediated microglia migration, involving F-actin redistribution.
Conclusions:
- This study establishes the electrotaxis of BV2 microglia.
- The ERK/GSK3β/cofilin pathway is essential for regulating microglia directional migration under DCEF.
- Findings provide novel insights into microglia behavior and potential therapeutic strategies for CNS disorders.
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