Researchers have identified RUVBL2 as a promising therapeutic target for mitigating post-operative delirium (POD) in older adults, a condition that significantly exacerbates cognitive decline. In a rat model of mild cognitive impairment, silencing the RUVBL2 gene led to improved cognitive outcomes following anaesthetic surgery, highlighting its role in the metabolic changes that occur in microglial cells within the hippocampus post-surgery.

The study reveals that surgery-induced stress activates microglia, leading to a metabolic shift from oxidative phosphorylation to glycolysis, which is associated with increased inflammation and cognitive deficits. Specifically, the pro-inflammatory cytokine IL-1β was elevated while the anti-inflammatory IL-10 was decreased in rats subjected to sevoflurane anaesthesia. These changes correlate with the formation of stress granules, which are detrimental in the context of neurodegeneration. By reducing RUVBL2 expression, researchers observed a decrease in inflammatory markers, a restoration of ATP levels, and improved performance in cognitive tests, suggesting that targeting RUVBL2 could counteract the negative cognitive effects of surgical stress.

The implications of this research are significant for the field of aging and cognitive health. By establishing RUVBL2 as a critical player in the pathophysiology of POD, this work paves the way for the development of therapeutic interventions that could protect cognitive function in older patients undergoing surgery. Future studies will need to address the heterogeneity of microglial responses and further elucidate the mechanisms by which RUVBL2 modulation can be harnessed to improve outcomes in this vulnerable population.

Source: lifespan.io