title: Trehalose protects from aggravation of amyloid pathology induced by isoflurane anesthesia in APP(swe) mutant mice.
abstract: There is an open controversy about the role of surgery and anesthesia in the pathogenesis of Alzheimer's disease (AD). Clinical studies have shown a high prevalence of these procedures in subjects with AD but the interpretation of these studies is difficult because of the co-existence of multiple variables. Experimental studies in vitro and in vivo have shown that small molecular weight volatile anesthetics enhance amyloidogenesis in vitro and produce behavioral deficits and brain lesions similar to those found in patients with AD. We examined the effect of co-treatment with trehalose on isoflurane-induced amyloidogenesis in mice. WT and APP(swe) mice, of 11 months of age, were exposed to 1% isoflurane, 3 times, for 1.5 hours each time and sacrificed 24 hours after their last exposure to isoflurane. The right hemi-brain was used for histological analysis and the contra-lateral hemi-brain used for biochemical studies. In this study, we have shown that repetitive exposure to isoflurane in pre-symptomatic mature APP(swe) mice increases apoptosis in hippocampus and cerebral cortex, enhances astrogliosis and the expression of GFAP and that these effects are prevented by co-treatment with trehalose, a disaccharide with known effects as enhancer of autophagy. We have also confirmed that in our model the co-treatment with trehalose increases the expression of autophagic markers as well as the expression of chaperones. Cotreatment with trehalose reduces the levels of β amyloid peptide aggregates, tau plaques and levels of phospho-tau. Our study, therefore, provides new therapeutic avenues that could help to prevent the putative pro-amyloidogenic properties of small volatile anesthetics.
authors.affiliation: Department of Neurobiology, Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Perucho
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Casarejos
authors.forename: Ana
authors.initials: A
authors.lastname: Gomez
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Solano
authors.forename: Justo Garcia
authors.initials: JG
authors.lastname: de Yébenes
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mena
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007530:Isoflurane / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014199:Trehalose / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D014199:Trehalose; D007530:Isoflurane