Potential Mechanism of Neurite Outgrowth Enhanced by Electrical Stimulation: Involvement of MicroRNA-363-5p Targeting DCLK1 Expression in Rat

Electrical stimulation (ES) promotes neurite outgrowth and nerve regeneration, but the underlying mechanisms remain undefined. In the present study, we investigated the role of micro RNAs (miRNAs) in ES-mediated neurite outgrowth. First, we performed microarray analyses to identify changes in the miRNAs profile of dorsal root ganglion neurons (DRGNs) following ES. The expression of 16 known miRNAs was altered by ES. Bioinformatics showed that the potential targets of these differentially expressed miRNAs were involved in neurite outgrowth. We focused on miRNA-363-5p (miR-363-5p), because its expression was consistently altered by ES in the present study. Silencing miR-363-5p promoted neurite outgrowth, while miR-363-5p mimic reduced neurite outgrowth. Downregulation of miR-363-5p indicated that double cortin-like kinase (DCLK) 1, a major microtubule-associated protein, was a direct target of miR-363-5p in DRGNs. Knockdown of DCLK1 recapitulated the beneficial effect of a miR-363-5p inhibitor on DRG neurite outgrowth. In conclusion, our data has indicated that miR-363-5p is involved in ES-promoted neurite outgrowth by targeting DCLK1. These findings provide new insights into the roles of miRNAs in ES-enhanced neurite outgrowth and regeneration.