The potential dual effects of sevoflurane on AKT/GSK3β signaling pathway

BACKGROUND Anesthesia with multiple exposures of commonly used inhalation anesthetic sevoflurane induces neuroinflammation and cognitive impairment in young mice, but anesthesia with a single exposure to sevoflurane does not. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway is involved in neurotoxicity and neurobehavioral deficits. However, whether sevoflurane can induce a dual effect (increase versus decrease) on the activation of AKT/GSK3β signaling pathway remains to be determined. We therefore set out to assess the effects of sevoflurane on AKT/GSK3β signaling pathway in vivo and in vitro. METHODS Six day-old wild-type mice were exposed to 3% sevoflurane two hours daily for one or three days. In the in vitro studies, H4 human neuroglioma cells were treated with 4% sevoflurane for two or six hours. We then determined the effects of different sevoflurane treatments on the levels of phosphorylated (P)-GSK3β(ser9) and P-AKT(ser473) by using Western blot analysis. RESULTS Here we show that anesthesia with 3% sevoflurane two hours daily for one day increased the levels of P-GSK3β(ser9) and P-AKT(ser473), but the anesthesia with 3% sevoflurane daily for three days decreased them in the mice. The treatment with 4% sevoflurane for two hours increased, but the treatment with 4% sevoflurane for six hours decreased, the levels of P-GSK3β(ser9) and P-AKT(ser473) in the H4 human neuroglioma cells. CONCLUSIONS Anesthetic sevoflurane might induce a dual effect (increase versus decrease) on the activation of the AKT/GSK3β signaling pathway. These studies have established a system to perform further studies to determine the effects of sevoflurane on brain function.