Post-operative cognitive dysfunction (POCD) is the persistent form of post-operative delirium, a noticeable deterioration in cognitive abilities that occurs abruptly following surgery. POCD has been largely associated with older individuals, posing an increased risk for the development of Alzheimer’s disease (AD). Emerging evidence suggests that pre-operative lifestyle factors, including exercise, may influence susceptibility to POCD and AD. It is known that laparotomy (exploratory abdominal surgery) combined with opioid treatment (for pain management) in aged rats produces memory impairments lasting at least 8 weeks, alongside region specific mitochondrial dysfunction. Thus, the purpose of this study was to utilize an acute bout of exercise to mitigate POCD in a mouse model of AD. Mice underwent 3 weeks of voluntary wheel running prior to surgery and morphine. Laparotomies were performed on 3xTg-AD mice at 9 months old followed by 7 days of morphine administration (2mg/kg, i.p., based on our previous work in rats). A battery of cognitive behavioral tests were performed 2 weeks post-surgery. Our findings demonstrated that exercise ameliorated impairments in prefrontal cortex-dependent executive function and hippocampal-dependent memory assessed by nesting and the contextual fear test, respectively. The behavioral improvements were accompanied by a notable decrease in amyloid beta (AB42) in the hippocampus of the exercise + morphine-treated mice compared to sedentary controls, as measured by an ELISA assay. We then examined mitochondrial function in freshly isolated mitochondria from hippocampus using the Seahorse Analyzer XFe96. Exercise + morphine-treated mice demonstrated a significant increase in basal and maximal respiration compared to the sedentary + morphine-treated mice, indicating a rescue in mitochondrial function. In conclusion, in 3xTg-AD mice, a pre-operative bout of exercise reduced post-operative cognitive deficits, attenuated AD-related pathology, and restored mitochondrial function. These findings suggest that exercise may serve as a non-pharmacological strategy to mitigate POCD, potentially through preservation of mitochondrial health. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Blackwell et al. (Fri,) studied this question.