title: Potential protective effect of biphasic electrical stimulation against growth factor-deprived apoptosis on olfactory bulb neural progenitor cells through the brain-derived neurotrophic factor-phosphatidylinositol 3'-kinase/Akt pathway.
abstract: Stem cell therapy may provide a therapeutic method for the replacement and regeneration of damaged neurons of the central nervous system. However, neural stem cells (NSCs) and neural precursor cells (NPCs) are especially vulnerable after transplantation due to a lack of sufficient growth factors at the transplant site. Electrical stimulation (ES) has recently been found to participate in the regulation of cell proliferation, growth, differentiation, and migration, but its underlying anti-apoptotic effects remain unclear. This study investigated the protective effects of biphasic electrical stimulation (BES) on olfactory bulb NPCs against growth factor-deprived apoptosis, examining the survival and apoptotic features of the cells. Differentiation was assessed by neuronal and glial markers. Brain-derived neurotrophic factor-phosphatidylinositol 3'-kinase (BDNF)-PI3K/Akt pathway activation was determined by enzyme-linked immunosorbent assay and Western blot. The chemical inhibitor wortmannin was used to inhibit the PI3K/Akt pathway. BES exerts a protective effect against growth factor-deprived apoptosis in the NPCs. BES enhanced cell survival and decreased the apoptotic/necrotic rate. Expression of phosphorylated Akt and BDNF secretion increased with BES for 12 h. Furthermore, the protective effects of BES were inhibited by blocking PI3K/AKT signalling. These results suggest that BES prevents growth factor-deprived apoptosis through the BDNF-PI3K/Akt signalling. This work strengthens the opinion that BES may be used as an auxiliary strategy for improving cell survival and preventing cell apoptosis in stem cell-based transplantation therapy.
authors: School of Biological Science and Medical Engineering, Beihang University, Hai Dian District 100191, Beijing, China.
authors: Menghang
authors: M
authors: Wang
authors: Ping
authors: P
authors: Li
authors: Meili
authors: M
authors: Liu
authors: Wei
authors: W
authors: Song
authors: Qian
authors: Q
authors: Wu
authors: Yubo
authors: Y
authors: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004599:Electric Stimulation Therapy / Q000379:methods*; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency; D058953:Neural Stem Cells / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D009830:Olfactory Bulb / Q000473:pathology* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: BDNF-PI3K/Akt pathway; biphasic electrical stimulation; growth factor-deprived apoptosis; neural precursor cells; stem cell therapy