title: Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3β signaling pathway in a rat model of post-traumatic stress disorder.
abstract: OBJECTIVE
  Post-traumatic stress disorder (PTSD) is a psychiatric disease that may occur after intense psychological trauma or physiological stress. Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) and the serine/threonine kinase (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway are critically involved in brain plasticity, including hippocampal-dependent learning and memory, while sevoflurane impairs memory processing. Thus, we hypothesized that sevoflurane can suppress fear learning by regulating the expression of BDNF and the Akt/GSK-3β signaling pathway in a rat model of PTSD.
  
  
  METHODS
  Rats were exposed to sevoflurane during or after a 15 foot-shock stressor. Thereafter, rats were subjected to a single foot-shock in a totally different environment. The fear response was recorded in response to the 15 foot-shock and the single foot-shock environments. In another set of experiments, the brain tissue was harvested and subjected to biochemistry studies.
  
  
  RESULTS
  Our data suggested that increasing sevoflurane concentrations decreased stress-enhanced fear learning (SEFL) when given during but not after the stressor. Furthermore, administration of lithium chloride (100 mg/kg, intraperitoneally) 30 min before the contextual fear conditioning reversed the inhibitory effect of 0.8 % sevoflurane on SEFL as well as phosphorylated (p)-Akt, p-GSK-3β and BDNF expressions.
  
  
  CONCLUSIONS
  Our data suggested that increasing sevoflurane administration during but not after the stressor can impair SEFL in a rat model of PTSD, which may be due, at least in part, to the regulation of hippocampal BDNF expression and the Akt/GSK-3β signaling pathway.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Chen
authors.forename: Muhuo
authors.initials: M
authors.lastname: Ji
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Sihai
authors.initials: S
authors.lastname: Zhu
authors.forename: Weiyan
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004195:Disease Models, Animal; D005239:Fear / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008738:Methyl Ethers; D000077149:Sevoflurane; C579455:BDNF protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3