title: The gender difference in effect of sevoflurane exposure on cognitive function and hippocampus neuronal apoptosis in rats.
abstract: OBJECTIVE
  Anesthesia and surgery can induce postoperative cognitive dysfunction. Ser-133 phosphorylation sites of cAMP-response element binding protein (CREB) is a key gene that mediate a variety of downstream transcription initiation factors, regulate neuronal survival and promote the expression of a large number of genes. Thus, CREB may play a role in this impairment. We hypothesize that and sevoflurane-induced cognitive impairment possibly via inhibiting the expression of CREB downstream genes and proteins.
  
  
  METHODS
  To test this hypothesis, adult Sprague-Dawley rats were subjected to sevoflurane exposure and were tested with a series of behavioral experiments (open field, passive avoidance test and Morris water maze test) at different time (1 d to 95 d). Besides, blood gas changes and expiratory sevoflurane concentrations were examined at 2 h; the levels of phosphorylated CREB 1, the protein Bcl-2, Caspase-8 and Caspase-3 were assessed at 1 week and 3 months after anesthesia. We also conducted a comparison in sevoflurane-induced cognitive impairment between male and female rats.
  
  
  CONCLUSIONS
  Here, we found that sevoflurane anesthesia can impair short-term cognitive function, which may be via down-regulating p-CREB1 and Bcl-2 expression and up-regulating Caspase-8 expression to reduce hippocampus neuronal apoptosis, and male rats suffered a more severe cognitive dysfunction than female rats. In addition, sevoflurane can produce a reversible long-term cognitive dysfunction in rats.
authors.affiliation: Department of Anesthesiology, The Second Affiliate Hospital of Soochow University, Suzhou, China. chenwangcn@yeah.net.
authors.forename: H
authors.initials: H
authors.lastname: Xie
authors.forename: G-M
authors.initials: GM
authors.lastname: She
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: L-Y
authors.initials: LY
authors.lastname: Zhang
authors.forename: C-F
authors.initials: CF
authors.lastname: Liu
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D012727:Sex Characteristics
chemical_list: D018685:Anesthetics, Inhalation; D017362:Cyclic AMP Response Element-Binding Protein; D008738:Methyl Ethers; D000077149:Sevoflurane; D053148:Caspase 3