Resveratrol Mitigates Hippocampal Tau Acetylation and Cognitive Deficit by Activation SIRT1 in Aged Rats following Anesthesia and Surgery.

ABSTRACT

Postoperative cognitive dysfunction (POCD) is a sever postsurgical neurological complication in the elderly population. As the global acceleration of population ageing, POCD is proved to be a great challenge to the present labor market and healthcare system. In the present study, our findings showed that tau acetylation mediated by SIRT1 deficiency resulted in tau hyperphosphorylation in the hippocampus of the aged POCD model and consequently contributed to cognitive impairment. Interestingly, pretreatment with resveratrol almost restored the expression of SIRT1, reduced the levels of acetylated tau and hyperphosphorylated tau in the hippocampus, and improved the cognitive performance in the behavioral tests. What is more, we observed that microglia-derived neuroinflammation resulting from SIRT1 inhibition in microglia probably aggravated the tau acetylation in cultured neurons in vitro. Our findings supported the notion that activation SIRT1 provided dually beneficial effect in the aged POCD model. Taken together, our findings provided the initial evidence that tau acetylation was associated with cognitive impairment in the aged POCD model and paved a promising avenue to prevent POCD by inhibiting tau acetylation in a SIRT1-dependent manner.