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Interplanetary exploration will be humankind’s most ambitious expedition and the journey required to do so, is as intimidating as it is intrepid. One major obstacle for successful deep space travel is the negative effects of galactic cosmic radiation (GCR) exposure. Here, we investigate how GCR impacts long-term behavioral and cellular responses in male and female mice. We find that a single exposure to GCR can induce long-term behavioral deficits in male cohorts, characterized by diminished social interaction, increased anxiety-like phenotype and impaired recognition memory. Remarkably, we find that the female cohorts did not display any behavioral deficits caused by GCR exposure. Mechanistically, we identify that the maladaptive behavioral responses in the male, GCR-exposed cohorts correspond with microglia activation and synaptic loss in the hippocampus, a brain region involved in the cognitive domains reported here. Furthermore, we measured reductions in AMPA expressing synaptic terminals measured in the hippocampus. Taken together these findings suggest that GCR exposure can regulate microglia activity and alter synaptic architecture which in turn leads to a range of cognitive alterations. These novel results identify sex-dependent differences in cognitive domains revealing promising cellular and molecular intervention targets to reduce GCR-induced chronic cognitive deficits. Improved understanding of these differences boosts chances of success for humans in deep space missions such as the upcoming Mars voyage.

In previous experiments, we have shown that spaceflight can alter leukocyte and lymphocyte population distributions and mitogen-induced cytokine expression. We hypothesize that these changes are a result of flight-induced physiological and psychological stress. On July 8, 2011, age- and weight-matched, female C57BL/6J mice were placed into Animal Enclosure Modules (AEMs) and flown on the Space Shuttle Atlantis (STS-135) for 13 days ( N = 6–7). Ground controls were housed at the Space Life Science Laboratory (SLSL) at Kennedy Space Center (KSC). Ground AEM control mice were placed into the same hardware used in flight and environmental parameters such as temperature and CO2 levels were matched as closely as possible based on 48 h delayed telemetry data ( N = 12–13). Vivarium control mice were housed in regular shoebox cages ( N = 4). Mice were euthanized and dissected within 3–5 h of landing. Adrenals were removed, snap frozen in liquid N2, and shipped on ice back to Loma Linda University via overnight courier for analysis. Although corticosterone levels were slightly elevated in spaceflight mice, with a corresponding decrease in phosphorylated adrenocorticotropic hormone (ACTH) levels, these changes were not enough to reach significance. Similarly, there were no significant changes in catecholamine levels. This suggests that there is no significant impact of spaceflight on stress pathways. However, closer examination of the data indicates that the circadian rhythm may have masked the overall effect of spaceflight.