title: Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice.
abstract: OBJECTIVE
  This study explored whether surgical stress-induced glucocorticoid receptor (GR) phosphorylation is related to postoperative cognitive dysfunction (POCD) in aged individuals. Inhibition of GR activation could be an effective treatment for POCD.
  
  
  METHODS
  A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6 months old. Animals in control group were treated in identical manners except for laparotomy. Cognitive function was evaluated by Morris water maze and elevated plus maze. Western blot and Elisa assay were used to detect related molecules. Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation.
  
  
  RESULTS
  The cognitive function was impaired, and brain-derived neurotrophic factor (BDNF) was found reduced in aged POCD group. GR translocation into nucleus and elevated GR phosphorylation were found in prefrontal cortex of aged POCD mice. Cyclin-dependent Kinase 5 (CDK5), kinase for GR phosphorylation also elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of BDNF and cognitive dysfunction in aged mice were both rescued.
  
  
  CONCLUSIONS
  These results presented a mechanism that surgical stress-induced GR phosphorylation contributes to POCD in aged individuals. Inhibition of GR activation and phosphorylation might be a potential treatment target of POCD.
authors.affiliation: Neuroscience Research Institute & Department of Neurobiology; Health Science Center, Peking University, Beijing, China; Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors.forename: Xiao-Sheng
authors.initials: XS
authors.lastname: Tian
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Tong
authors.forename: Zheng-Qian
authors.initials: ZQ
authors.lastname: Li
authors.forename: Lun-Xu
authors.initials: LX
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Tian-Yun
authors.initials: TY
authors.lastname: Ren
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: He-Cheng
authors.initials: HC
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhan
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yan
authors.forename: Qiu-Dian
authors.initials: QD
authors.lastname: Wang
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Fan
authors.forename: Fan-Jun
authors.initials: FJ
authors.lastname: Kong
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Guo
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Xiao
authors.forename: De-Hua
authors.initials: DH
authors.lastname: Chui
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency*; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D011183:Postoperative Complications / Q000378:metabolism* / Q000523:psychology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011965:Receptors, Glucocorticoid; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse
keywords: Aging; Brain-derived neurotrophic factor (BDNF); GR phosphorylation; Postoperative cognitive dysfunction (POCD); Surgical stress