title: Isoflurane exposure during mid-adulthood attenuates age-related spatial memory impairment in APP/PS1 transgenic mice.
abstract: Many in vitro findings suggest that isoflurane exposure might accelerate the process of Alzheimer Disease (AD); however, no behavioral evidence exists to support this theory. In the present study, we hypothesized that exposure of APP/PS1 transgenic mice to isoflurane during mid-adulthood, which is the pre-symptomatic phase of amyloid beta (Abeta) deposition, would alter the progression of AD. Seven-month-old Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mice and their wild-type littermates were exposed to 1.1% isoflurane for 2 hours per day for 5 days. Learning and memory ability was tested 48 hours and 5 months following isoflurane exposure using the Morris Water Maze and Y maze, respectively. Abeta deposition and oligomers in the hippocampus were measured by immunohistochemistry or Elisa 5 months following isoflurane exposure. We found that the performance of both the transgenic and wild-type mice in the Morris Water Maze significantly improved 48 hours following isoflurane exposure. The transgenic mice made significantly fewer discrimination errors in the Y maze following isoflurane exposure, and no differences were found between wild-type littermates 5 months following isoflurane exposure. For the transgenic mice, the Abeta plaque and oligomers in the hippocampus was significantly decreased in the 5 months following isoflurane exposure. In summary, repeated isoflurane exposure during the pre-symptomatic phase not only improved spatial memory in both the APP/PS1 transgenic and wild-type mice shortly after the exposure but also prevented age-related decline in learning and memory and attenuated the Abeta plaque and oligomers in the hippocampus of transgenic mice.
authors.affiliation: Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Diansan
authors.initials: D
authors.lastname: Su
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.forename: Beilei
authors.initials: B
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053764:Presenilin-1 / Q000235:genetics; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D016564:Amyloid beta-Protein Precursor; D018685:Anesthetics, Inhalation; D053764:Presenilin-1; D007530:Isoflurane