Abstract
BackgroundPostoperative cognitive dysfunction (POCD) seriously reduces quality of life and is associated with increased morbidity and mortality. The causes and neuropathogenesis of POCD remain largely unknown. Resveratrol, a sirtuin 1 (Sirt1) activator, is a polyphenol compound found in red wine that has protective functions in neuropathology paradigms. Endoplasmic reticulum stress (ERS) is a primary cellular response that activates the unfolded protein response (UPR). ERS and UPR mediate molecular and biochemical mechanisms related to neurodegeneration; however, the roles of ERS and Sirt1 in POCD remain unclear. The properties of resveratrol might be useful in the setting of POCD.MethodsIn the present study, we investigated learning and memory function and ERS pathways in aged mice after surgery under local anesthesia, and we evaluated the effects of resveratrol pretreatment.ResultsWe found that resveratrol attenuated postoperative learning and memory impairment in aged mice postoperatively but did not alter locomotor activity. Resveratrol significantly decreased postoperative expression of ERS pathway UPR-related proteins and inflammatory mediators including nuclear factor-κB (NF-κB) in the hippocampus. This was accompanied by higher Sirt1 protein expression levels. Pretreatment with resveratrol did not affect the number of hippocampal neurons in aged mice after surgery.ConclusionOverall, resveratrol pretreatment attenuated short-term learning and memory impairment and the ERS pathway UPR in aged mice after surgery under local anesthesia.
Highlights
Postoperative cognitive dysfunction (POCD) seriously reduces quality of life and is associated with increased morbidity and mortality
Pretreatment with resveratrol attenuated the POCD in aged mice Compared with the control group, the freezing times for both the context and tone tests at 24 h, 48 h, and 7 days postoperatively were significantly decreased in the surgery group
The freezing times of the resveratrol group were significantly higher than that of surgery group (Fig. 2a and b). These results indicated that pretreatment with resveratrol attenuated learning and memory impairment in aged mice
Summary
Postoperative cognitive dysfunction (POCD) seriously reduces quality of life and is associated with increased morbidity and mortality. Endoplasmic reticulum stress (ERS) is a primary cellular response that activates the unfolded protein response (UPR). Aged patients are prone to postoperative decreases in learning and memory function, resulting in decreased quality of life and increased social burden [1,2,3]. Improvements of anesthesia and surgical techniques have led to larger numbers of older patients receiving anesthesia and surgery. These patients are more likely to exhibit postoperative learning and memory impairment. Improving postoperative cognitive function and preventing postoperative cognitive dysfunction (POCD) are therefor of great significance. ERS has been linked with cognitive function in inhaled anesthetics-induced cognitive dysfunction and neurodegenerative conditions
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