title: Isoflurane-induced spatial memory impairment by a mechanism independent of amyloid-beta levels and tau protein phosphorylation changes in aged rats.
abstract: OBJECTIVE
  The molecular mechanism of postoperative cognitive dysfunction is largely unknown. Isoflurane has been shown to promote Alzheimer's disease neuropathogenesis. We set out to determine whether the effect of isoflurane on spatial memory is associated with amyloid-beta (A-beta) levels and tau phosphorylation in aged rats.
  
  
  METHODS
  Eighteen-month-old male Sprague-Dawley rats were randomly assigned as anesthesia group (n = 31, received 1.4% isoflurane for 2 hours and had behavioral testing), training group (n = 20, received no anesthesia but had behavioral testing), and control group (n = 10, received no anesthesia and had no behavioral testing). Spatial memory was measured before and 2 days after the anesthesia by the Morris water maze. We divided the anesthesia group into an isoflurane-induced severe memory impairment group (SIG, n = 6) and a no severe memory impairment group (NSIG, n = 25), according to whether the escape latency was more than 1.96 stand deviation of that from the training group. Levels of A-beta and tau in the hippocampus were determined by enzyme-linked immunosorbent assay and quantitative western blot at the end of behavioral testing.
  
  
  RESULTS
  We found that isoflurane increased the escape latency in the SIG as compared to that in the training group and NSIG without affecting swimming speed. However, there were no differences in the levels of A-beta and tau among SIG, NSIG, training, and control groups.
  
  
  CONCLUSIONS
  Isoflurane may induce spatial memory impairment through non-A-beta or tau neuropathogenesis mechanisms in aged rats.
authors.affiliation: Department of Anesthesia, Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Weiran
authors.initials: W
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Chengshi
authors.initials: C
authors.lastname: Xu
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Feng
authors.forename: Xuena
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Anshi
authors.initials: A
authors.lastname: Wu
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie
authors.forename: Yun
authors.initials: Y
authors.lastname: Yue
mesh_terms: D000375:Aging / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D008568:Memory / Q000187:drug effects*; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D016875:tau Proteins; D007530:Isoflurane