Abstract # 3119 I am woman, watch me soar: females protected from cosmic ray-induced behavioral deficits, microglia activation and synaptic loss

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.