Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

Abstract

BackgroundHypoxic-ischemic brain damage (HIBD) significantly affects neurodevelopment in infants and is a leading cause of severe neurological morbidity and mortality in neonates. Our previous study found that photobiomodulation therapy (PBMT) improves the impaired spatial learning and memory of HIBD rat models. However, the neuroprotective mechanism conferred by PBMT in HIBD is unclear.MethodsIn the present study, HIBD model rats were treated with PBMT at 5 mW/cm2 per day in the dark for 14 days (10 min each day), and primary neural stem cells (NSCs) after oxygen-glucose deprivation (OGD) were treated with PBMT for 10 min at 1, 5, 10, and 20 mW/cm2 in the dark. PBMT promoted hippocampal neural stem cell (NSC) proliferation in vivo and in vitro.ResultsMechanistically, PBMT upregulated phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β), β-catenin, and cyclin D1 expression in vivo and in vitro, promoting NSC proliferation. Furthermore, both LY294002 (a PI3K inhibitor) and IWR-1 (a Wnt/β-catenin inhibitor) inhibited the PBMT promotion of NSC proliferation after OGD and suppressed β-catenin and cyclin D1 expression in vitro.ConclusionsPBMT improved the spatial learning and memory of HIBD rats and promoted hippocampal NSC proliferation through the AKT/GSK-3β/β-catenin pathway.