Modulation of gap junction-associated Cx43 in neural stem/progenitor cells following traumatic brain injury

Restoration of learning and memory deficits following traumatic brain injury (TBI) is attributed, in part, to enhanced neural stem/progenitor cell (NSPCs) function. Recent findings suggest gap junction (GJ)-associated connexin 43 (Cx43) plays a key role in the cell cycle regulation and function of NSPCs and is modulated following TBI. Here, we demonstrate that Cx43 is up-regulated in the dentate gyrus following TBI and is expressed on vimentin-positive cells in the subgranular zone. To test the role of Cx43 on NSPCs, we exposed primary cultures to the alpha-connexin Carboxyl Terminal (alpha CT1) peptide which selectively modulates GJ-associated Cx43. Treatment with alpha CT1 substantially reduced proliferation and increased caspase 3/7 expression on NSPCs in a dose-dependent manner. alpha CT1 exposure also reduced overall expression of Cx43 and phospho (p)-Serine368. These findings demonstrate that Cx43 positively regulates adult NPSCs; the modulation of which may influence changes in the dentate gyrus following TBI.