title: The hippocampal cyclin D1 expression is involved in postoperative cognitive dysfunction after sevoflurane exposure in aged mice.
abstract: OBJECTIVE
  Increasing evidence has suggested cognitive impairment and neuronal apoptosis induced by anaesthetics are due to abnormal hyperphosphorylation of tau protein, but the detailed mechanism remains unknown.
  
  
  METHODS
  Aged mice and neurons were both exposed to 2.5% sevoflurane for 2h. Spatial learning ability of the aged mice was tested with Morris water maze. The changes of neuroapoptosis, tau protein and cell-cycle-related factors (cyclin D1, p27) were determined using Western blot analysis. The effect of sevoflurane exposure on DNA synthesis was tested with immunofluorescent staining.
  
  
  RESULTS
  We found that sevoflurane significantly impaired spatial learning ability in aged mice. In addition, total tau protein. phosphorylated tau protein, Caspase-3 and cyclin D1, but not p27Kip1 were drastically increased in the hippocampus. Consistent with the results from in vivo study, sevoflurane significantly increased the expression of cyclin D1 and Brdu positive neurons in cultured hippocampal neurons. The enhancement of cyclin D1 was partially reversed by the pharmacological inhibition of hyperphosphorylation of tau.
  
  
  CONCLUSIONS
  Our results suggested that cyclin D1 overexpression may result in the neuronal apoptosis through cell cycle re-entry and the deficits in postoperative cognitive dysfunction after sevoflurane exposure. Our research will improve the current understanding of the mechanisms underlying the postoperative cognitive dysfunction by anaesthetics exposure.
authors.affiliation: Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Anaesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ling
authors.affiliation: Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Song
authors.affiliation: Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China.
authors.forename: Qiuaxue
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, 130 Dongan Rd, Shanghai 200032, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lai
authors.affiliation: Department of Anaesthesiology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032, China. Electronic address: cangjing_zs@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Cang
mesh_terms: D000375:Aging; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003072:Cognition Disorders / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018782:Maze Learning; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011184:Postoperative Period; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D019938:Cyclin D1; D000077149:Sevoflurane
keywords: Cyclin D1; Hippocampus; Postoperative cognitive dysfunction; Sevoflurane; Spatial memory impairment