Electrical Stimulation Induces Calcium-Dependent Neurite Outgrowth and Immediate Early Genes Expressions of Dorsal Root Ganglion Neurons

It has been reported that electrical stimulation (ES) can promote nerve regeneration. One of the key factors leading to the promotion is calcium, which plays a vital role in the regulation on electrical activity of neurons, but the detailed mechanism is still an open question. In this study, ES was used to stimulate cultured dorsal root ganglion neurons (DRGNs) and we've found that ES could greatly promote neurite outgrowth, and calcium signaling was involved in the ES-induced neurite extension in our research. Detailed pharmacological tests indicated that ES-induced elevation of intracellular free calcium concentration ([Ca2+] (i) ) in DRGNs was realized predominately via calcium influx and calcium mobilization, both of which contributed to enhancing neurite outgrowth promoted by ES. Additionally, a calcium-triggered c-fos and brain-derived neurotrophic factor (BDNF) transcription and/or translation were discovered during the ES-induced neurite outgrowth of cultured DRGNs. To our knowledge, this is the first case of detailed snapshots of studying calcium-dependent neurite outgrowth and BDNF and c-fos expressions in DRGNs induced by ES, which may provide experimental evidence for applying ES to promote regeneration of injured nerves and to enhance synthesis of c-fos and BDNF in neurons, and may also help explore the complex molecular cascades underlying the progressive pathophysiological changes in the ES-induced nerve regeneration in future.