SOX5 Attenuates Toxicity in Neural Stem Cells Induced by Sevoflurane Anesthesia via Regulating the PI3K/AKT Pathway

Abstract

Differentiation and self-renewal capacity of neural stem cells are essential for the development and function of brain. Anesthesia exposure inhibits the differentiation and self-renewal capacity of neural stem cells, impairs neurological function during the development of brain. SOX5 exerted neuroprotective effect against ischemic stroke, and regulated chondrogenic differentiation of stem cells. However, the effect and mechanism of SOX5 on sevoflurane-induced neurotoxicity of neural stem cells have not been reported. Firstly, neural stem cells were isolated from hippocampus of neonatal rats. Results showed that the neural stem cells formed neurospheres, and expressed NESTIN. The isolated neural stem cells were then exposed to sevoflurane anesthesia. Sevoflurane exposure reduced expression of NESTIN, decreased cell viability and suppressed cell proliferation of neural stem cells, thus inhibiting the differentiation and self-renewal capacity of neural stem cells. Secondly, SOX5 was down-regulated in sevoflurane-induced neural stem cells. Over-expression of SOX5 enhanced cell viability of sevoflurane-induced neural stem cells, and promoted the cell proliferation. Moreover, sevoflurane induced cell cycle arrest at G0/G1 phase and promoted the cell apoptosis in neural stem cells. Over-expression of SOX5 attenuated sevoflurane-induced increase of G0/G1 ratio and apoptosis in neural stem cells. Thirdly, sevoflurane-induced decrease of phosphorylated PI3K (p-PI3K) and p-AKT expression in neural stem cells were reversed by SOX5 over-expression. In conclusion, SOX5 attenuated sevoflurane-induced toxicity in neural stem cells through inactivation of PI3K/AKT pathway.