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. VT's Institute of Critical Technology and Science; Virginia Maryland College of Veterinary Medicine; [R01 NS096281]; [NS096281]; [R15 NS081623] The authors would like to thank VT-IMSD Programs for student support (K.M.G.). This work was supported by R01 NS096281 (MHT), diversity supplement NS096281 (MHT, KG), R15 NS081623 (MHT) and VT's Institute of Critical Technology and Science. We recognize the Virginia Maryland College of Veterinary Medicine for student and financial support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or any other funding agency.