Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia

Emmanuel Planel, Alexis Bretteville, Li Liu, Laszlo Virag, Angela L. Du, Wai Haung Yu, Dennis W. Dickson, Robert A. Whittington, Karen E. Duff

Research output: Contribution to journalArticle

92 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2595-2604
Number of pages10
JournalFASEB Journal
Volume23
Issue number8
DOIs
StatePublished - Aug 2009

Keywords

  • Alzheimer's disease
  • Hypothermia
  • Microtubules
  • Tau hyperphosphorylation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Planel, E., Bretteville, A., Liu, L., Virag, L., Du, A. L., Yu, W. H., Dickson, D. W., Whittington, R. A., & Duff, K. E. (2009). Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. FASEB Journal, 23(8), 2595-2604. https://doi.org/10.1096/fj.08-122424