Weightlessness, as experienced during space travel or prolonged bed rest, has been associated with various physiological changes, including alterations in metabolism and cognition. However, the impact of weightlessness on hippocampal insulin sensitivity and cognitive function remains poorly understood. In this study, we investigated the effects of simulated weightlessness on hippocampal insulin resistance and cognitive performance in a rodent model. Male rats were subjected to hindlimb unloading (HU) to simulate weightlessness for 21 days, while control rats remained weightbearing. Our findings reveal that simulated weightlessness induced hippocampal insulin resistance, as evidenced by impaired insulin signaling and reduced glucose uptake in the hippocampi of HU rats compared to controls. Additionally, HU rats exhibited deficits in spatial learning and memory tasks, indicative of cognitive impairment. These results suggest that weightlessness may contribute to hippocampal insulin resistance and cognitive dysfunction, highlighting the importance of further investigation into the mechanisms underlying these effects. Understanding the impact of weightlessness on brain metabolism and cognition is crucial for developing strategies to mitigate the adverse effects of space travel and prolonged bed rest on neurological health
