title: Anesthesia in presymptomatic Alzheimer's disease: a study using the triple-transgenic mouse model.
abstract: BACKGROUND
  Experimental evidence suggests that anesthetics accelerate symptomatic neurodegenerative disorders such as Alzheimer's disease (AD). Because AD pathology precedes symptoms, we asked ourselves whether anesthetic exposure in the presymptomatic interval accelerated neuropathology and appearance of symptoms.
  
  
  METHODS
  Triple-transgenic AD mice were exposed to general aesthetics, either halothane or isoflurane, at 2, 4, and 6 months of age, they then underwent water maze cognitive testing 2 months later, and subsequently their brains were analyzed using enzyme-linked immunosorbent assay, immunoblots, and immunohistochemistry for amyloid and tau pathology and biomarkers.
  
  
  RESULTS
  Learning and memory improved after halothane exposure in the 2-month-old group relative to controls, but no changes were noted in the isoflurane group. When gender was examined in all age groups, females exposed to halothane performed better as compared with those exposed to isoflurane or controls. Therefore, improvement in the 2-month exposure group is most likely because of a gender effect. Level of phospho-tau in the hippocampus was significantly increased 2 months after anesthesia, especially in the 6-month exposure group, but changes in amyloid, caspase, microglia, or synaptophysin levels were not detected.
  
  
  CONCLUSIONS
  These results indicate that exposure to two different inhalation-type anesthetics during the presymptomatic phase of AD does not accelerate cognitive decline, after 2 months, and may cause a stress response, marked by hippocampal phosphorylated tau, resulting in preconditioning against the ongoing neuropathology, primarily in female mice.
authors: Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors: Junxia X
authors: JX
authors: Tang
authors: Feras
authors: F
authors: Mardini
authors: Breanna M
authors: BM
authors: Caltagarone
authors: Sean T
authors: ST
authors: Garrity
authors: Rosie Q
authors: RQ
authors: Li
authors: Shannon L
authors: SL
authors: Bianchi
authors: Olubusola
authors: O
authors: Gomes
authors: Frank M
authors: FM
authors: Laferla
authors: Roderic G
authors: RG
authors: Eckenhoff
authors: Maryellen F
authors: MF
authors: Eckenhoff
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D018685:Anesthetics, Inhalation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006221:Halothane / Q000008:administration & dosage; D007530:Isoflurane / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D006221:Halothane