Journal
CURRENT ALZHEIMER RESEARCH
Volume 9, Issue 3, Pages 334-343Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156720512800107573
Keywords
Amyloid pathology; apoptotic cell death; APP(swe) mice; autophagy chaperones; glial cells; isoflurane; trehalose
Categories
Funding
- Spanish Ministry of Health [FIS 2007/0037, FIS 2010/172, CAM 0202/2006, CIBER 2006/05/0059, CIBER 2010/05]
- CIBER
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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. Co-treatment with trehalose reduces the levels of beta 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.
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