Direct-current electrical fields (EFs) promote nerve growth and axon regeneration. We report here that, at physiological strengths, EFs guide the migration of neuronal stem/progenitor cells (NSPCs) towards cathode. EF-directed NSPC migration requires activation of N-methyl-D-aspartate receptors (NMDARs), which leads to an increased physical association of Rho GTPase Rac1-associated signals to the membrane NMDARs and the intracellular actin cytoskeleton. Thus, this study identifies the EF as adirectional guidance cue in controlling NSPC migration and reveals a role of the NMDAR/Rac1/actin signal transduction pathway in mediating EF-induced NSPC migration. These results suggest that as a safe physical approach in clinical application, EFs may be developed as a practical therapeutic strategy for brain repair by directing NSPC migration to the injured brain regions to replace cell loss.
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