Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia
- 11 March 2009
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 23 (8), 2595-2604
- https://doi.org/10.1096/fj.08-122424
Abstract
Alzheimer's disease and other tauopathies are characterized by the presence of intracellular neurofibrillary tangles composed of hyperphosphorylated, insoluble tau. General anesthesia has been shown to be associated with increased risk of Alzheimer's disease, and we have previously demonstrated that anesthesia induces hypothermia, which leads to overt tau hyperphosphorylation in the brain of mice regardless of the anesthetic used. To investigate whether anesthesia enhances the long-term risk of developing pathological forms of tau, we exposed a mouse model with tauopathy to anesthesia and monitored the outcome at two time points-during anesthesia, or 1 wk after exposure. We found that exposure to isoflurane at clinically relevant doses led to increased levels of phospho-tau, increased insoluble, aggregated forms of tau, and detachment of tau from microtubules. Furthermore, levels of phospho-tau distributed in the neuropil, as well as in cell bodies increased. Interestingly, the level of insoluble tau was increased 1 wk following anesthesia, suggesting that anesthesia precipitates changes in the brain that provoke the later development of tauopathy. Overall, our results suggest that anesthesia-induced hypothermia could lead to an acceleration of tau pathology in vivo that could have significant clinical implications for patients with early stage, or overt neurofibrillary tangle pathology.Keywords
Funding Information
- National Institute of Neurological Disorders and Stroke (NS048447)
- National Institute on Aging (AG017216)
This publication has 53 references indexed in Scilit:
- Anesthesia-Induced Hyperphosphorylation Detaches 3-Repeat Tau from Microtubules without Affecting Their StabilityIn VivoJournal of Neuroscience, 2008
- Co-localization of tau and α-synuclein in the olfactory bulb in Alzheimer’s disease with amygdala Lewy bodiesActa Neuropathologica, 2008
- The Common Inhalation Anesthetic Isoflurane Induces Apoptosis and Increases Amyloid β Protein LevelsAnesthesiology, 2006
- Tau Suppression in a Neurodegenerative Mouse Model Improves Memory FunctionScience, 2005
- Three- and Four-repeat Tau Regulate the Dynamic Instability of Two Distinct Microtubule Subpopulations in Qualitatively Different MannersJournal of Biological Chemistry, 2005
- The Role of Mitogen-Activated Protein Kinase Pathways in Alzheimer’s DiseaseNeurosignals, 2002
- Body temperature as a risk factor for Alzheimer’s diseaseMedical Hypotheses, 2000
- Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205Neuroscience Letters, 1995
- Early and Midlife Exposure to Anesthesia and Age of Onset of Alzheimer's DiseaseInternational Journal of Neuroscience, 1994
- Recognition of the minimal epitope of monoclonal antibody Tau‐1 depends upon the presence of a phosphate group but not its locationJournal of Neuroscience Research, 1993