Electric field application in vivo regulates neural precursor cell behavior in the adult mammalian forebrain

Abstract

Deep brain stimulation (DBS), which uses electrical stimulation, is a well-established neurosurgical technique used to treat neurologic disorders. Despite its broad therapeutic use, the effects of electrical stimulation on brain cells is not fully understood. Here, we examine the effects of electrical stimulation on neural stem and progenitor cells (collectively neural precursor cells; NPCs) from the subventricular zone in the adult forebrain of C57BL/6J mice. Previous work has demonstrated that adult-derived NPCs are electro sensitive and undergo rapid and directed migration in response to application of clinically relevant electric fields (EFs). We examine NPC proliferation kinetics and their differentiation profile following EF application using in vitro and in vivo assays. In vitro direct current electrical stimulation of 250 mV/mm is sufficient to elicit a 2-fold increase in the neural stem cell pool and increases neurogenesis and oligogenesis. In vivo, asymmetric biphasic electrical stimulation similarly increases the size of the NPC pool and alters neurogenesis. These findings provide insight into the effects of electrical stimulation on NPCs and suggest its potential use as a regenerative approach to neural repair.