ANESTHESIA-INDUCED TAU HYPERPHOSPHORYLATION IN MOUSE MODELS OF TAUOPATHY
- John D. Eun, United States of America
Abstract
Aims
Anesthesia in the elderly has been associated with subsequent cognitive decline. Although the mechanisms for this phenomenon are unclear, acute anesthesia exposure has been shown to increase tau hyperphosphorylation in rodent models. In order to further interrogate this relationship, we examined the long-term effects of anesthesia exposure on mouse models of tauopathy.
Methods
We exposed P301L, COMTKO/P301L, and hTau mice to isoflurane for two-hours without temperature control. In addition to ELISA and immunocytochemistry, we assessed gene expression changes in the brain using mRNA-seq in order to evaluate their association with tau hyperphosphorylation and pathology. In the hTau mouse, we examined spatial learning and memory of mice using the Barnes maze at baseline and 1-month and 7-months post-anesthesia.
Results
Across all three mouse models, the levels of phosphorylation at Thr231, Ser202, and Ser396/404 in the soluble fractions increased in the anesthesia group. However, 24-hours post-anesthesia, we did not observe a difference. At one-month post-anesthesia, we found elevated Thr231 hyperphosphorylation in the insoluble fraction in all three models. According to differential expression analysis, short- and long-term effects of acute hyperphosphorylation were different between the hTau mice and the mice with mutant human tau. We did not observe any differences in spatial learning and memory 1- or 7-months post-anesthesia.
Conclusions
Anesthesia was associated with acute hyperphosphorylation of tau in each model of tauopathy. Additionally, anesthesia induced short- and long-term changes in gene expression that may be associated with tau hyperphosphorylation.