title: The potential dual effects of sevoflurane on AKT/GSK3β signaling pathway.
abstract: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Dong
authors.forename: Celeste A
authors.initials: CA
authors.lastname: Swain
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th St,, Room 4310, Charlestown, MA 02129-2060, USA. zxie@mgh.harvard.edu.
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie