Gravity change differentially affects male and female cognition and anxiety-related parameters in mice

Variations in gravity affect multiple physiological and cognitive functions, therefore understanding how the body adapts to such changes is crucial, notably for space exploration. Astronauts exposed to altered gravity experience disturbances in sensory-motor functions, which are partly linked to vestibular system adaptations. Cognition and emotional regulation have been less studied and represent one of the most important challenges for long-term space missions. In this study, we examined the impact of exposure to 2G for 24 hours, 48 hours, or 15 days on locomotor activity, circadian rhythms, anxiety, blood corticosterone, sociability, short (spontaneous alternation) and long-term (object location memory OLM) memories in adult male and female C57BL/6JRj mice. While horizontal locomotion remains unchanged, vertical activity strongly decreases after short duration exposure (24h and 48h), but less after a longer duration (15d). Furthermore, exposure to 2G affects circadian rhythm synchronization during the first 24h after return to 1G, with males showing a time lag in activity cycles after 24h (peak activity occurs 5 hours later than in control mice) and females demonstrating a more rapid adaptation. Anxiety-like behavior increases for short duration exposure (24h) particularly in females, while blood corticosterone concentrations remain unchanged in all groups. Besides, sociability is affected in both sexes only after 48h of exposure. Short-term memory is altered after 24h exposure, but only in females whereas long-term memory is impaired in both sexes whatever the duration of 2G exposure. These findings provide new insights in the effects of HG exposure and its duration on behavioral abilities by 2G, with a particular sensitivity of recognition memory with a spatial component. They also highlight the importance of considering sex differences in gravitational adaptation and underline the need for targeted interventions to mitigate cognitive and physiological challenges for future space travels.