Applied electric fields activates endogenous neural stem and progenitor cells

Sefton, Elana1; Iwasa, Stephanie1; Rashidi, Abdolzim2; Popovic, Milos 1, 2; Morshead, Cindi1, 3

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3E1, Canada; 2. Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, M4G 3V9, Canada; 3. Department of Surgery, University of Toronto, Toronto, Ontario, M5S 3E1, Canada

Deep brain stimulation (DBS) is a well-established neurosurgical technique that is used to treat a variety of neurological disorders. Despite its broad use, the mechanisms underlying the effects of DBS remain unclear. Previous work by us and others have shown that electrical stimulation can enhance the migration of neural stem and progenitor cells (together termed neural precursor cells, NPCs) in the two neurogenic regions of the brain - the hippocampus and the subventricular zone. NPCs are electrosensitive cells that undergo rapid and directed migration in response to applied electric fields (EFs). We asked whether EF application altered the proliferation and fate of NPC, and have demonstrated that the number of murine neural stem cell derived colonies is increased following 1 hr of EF application (250mV/mm) in vitro.  The increased number of colonies could be due to a change in mode of neural stem cell division (promoting symmetric division) or enhanced neural stem cell survivival.  Further, we observed more neural stem cell colonies forming from mouse brains stimulated with the same strength EF for 1 hour, and examined 24 hours later.  This increase in neural stem cell colony number is consistent with a 50% increase in the number of proliferating cells in vivo. We are examining the fate of proliferative cells post-EF using markers of precursors and differentiated cells. These studies will provide insight into the mechanisms by which electrical stimulation through DBS regulates NPC behaviour in the CNS, towards the goal of enhancing efficacy and promoting neural repair.