title: Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics.
abstract: Inhaled anesthetics have been shown to increase the aggregation of amyloid beta in vitro through the stabilization of intermediate toxic oligomers, which are thought to contribute to neurocognitive dysfunction in Alzheimer's disease. Inhaled anesthetics may escalate cognitive dysfunction through enhancement of these intermediate oligomer concentrations. We intermittently exposed 12-month-old Tg2576 transgenic mice and nontransgenic littermates to isoflurane and halothane for 5 days. Cognitive function was measured before and after anesthetic exposures using the Morris Water Maze; amyloid beta plaque burden and caspase-3 mediated apoptosis were quantified by immunohistochemistry. At 12 months of age, anesthetic exposure did not further enhance cognitive decline in the transgenic mice. Immunohistochemistry, however, revealed that the halothane-exposed Tg2576 mice had more amyloidopathy than the isoflurane treated mice or the nonexposed transgenic mice. Isoflurane exposure impaired cognitive function in the nontransgenic mice, implying an alternative pathway for neurodegeneration. These findings indicate that inhaled anesthetics influence cognition and amyloidogenesis, but that the mechanistic relationship remains unclear.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, 305 John Morgan, 3620 Hamilton Walk, Philadelphia, PA 19104, USA. shannon.bianchi@uphs.upenn.edu
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Bianchi
authors.forename: Thuy
authors.initials: T
authors.lastname: Tran
authors.forename: Chuiliang
authors.initials: C
authors.lastname: Liu
authors.forename: Susan
authors.initials: S
authors.lastname: Lin
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Li
authors.forename: Jason M
authors.initials: JM
authors.lastname: Keller
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
authors.forename: Maryellen F
authors.initials: MF
authors.lastname: Eckenhoff
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000008:administration & dosage*; D007530:Isoflurane / Q000008:administration & dosage*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D007530:Isoflurane; D006221:Halothane