Physiological Electrical Signals Promote Chain Mig

Authors: Lin Cao Jin Pu Roderick H Scott Jared Ching Colin D McCaig

Publish Date: 2014/08/07

Volume: 11, Issue: 1, Pages: 75-86

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Abstract

Neuroblasts migrate as directed chains of cells during development and following brain damage A fuller understanding of the mechanisms driving this will help define its developmental significance and in the refinement of strategies for brain repair using transplanted stem cells Recently we reported that in adult mouse there are ionic gradients within the extracellular spaces that create an electrical field EF within the rostral migratory stream RMS and that this acts as a guidance cue for neuroblast migration Here we demonstrate an endogenous EF in brain slices and show that mimicking this by applying an EF of physiological strength switches on chain migration in mouse neurospheres and in the SHSY5Y neuroblastoma cell line Firstly we detected a substantial endogenous EF of 318 ± 45 mV/mm using microelectrode recordings from explants of the subventricular zone SVZ Pharmacological inhibition of this EF effectively blocked chain migration in 3D cultures of SVZ explants To mimic this EF we applied a physiological EF and found that this increased the expression of Ncadherin and βcatenin both of which promote cellcell adhesion Intriguingly we found that the EF upregulated P2Y purinoceptor 1 P2Y1 to contribute to chain migration of neuroblasts through regulating the expression of Ncadherin βcatenin and the activation of PKC Our results indicate that the naturally occurring EF in brain serves as a novel stimulant and directional guidance cue for neuronal chain migration via upregulation of P2Y1

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