Long-term effects of acute irradiation and isolation on crew age-matched mice

The future of space missions beyond low-Earth orbit presents exciting opportunities but may come with formidable health challenges. Astronauts face a unique combination of space stressors capable of exerting effects on the central nervous system (CNS) with possible sex-dependent differences. The interaction of these combined spaceflight stressors may induce oxidative stress, thereby altering brain integrity and behavioral performance. Understanding these changes is critical for safeguarding astronaut health and enabling successful exploration. By understanding the physiological responses to the combined effects of ionizing radiation (IR) and social isolation in the brain through immunohistochemistry (IHC), proteomics and cytokine expression analyses, we aim to identify CNS pathways ripe for countermeasure development to mitigate adverse brain changes with future deep space exploration. Here, we study the combined effects of simulated 5-ion galactic cosmic radiation (GCRsim) at acute dosage (5, 15, and 50 cGy) and social isolation on crew age-matched male and female mice at 124 days post-irradiation. We conducted analyses of hippocampal cytokine biomarkers and proteomic profiling on hippocampal lysates. Our findings reveal sex-specific regulation of hippocampal cytokines and proteomic profiles. Ongoing immunohistochemistry findings on the hippocampus will provide qualitative information regarding key protein expression and cellular changes such as microglial activation, blood brain barrier integrity, and neuroinflammation. With future plans for long-duration space missions, such as Mars exploration, understanding CNS changes over extended periods in mice can provide insights into potential long-term health impacts on astronauts. This project will provide us with valuable insights into sex-differences in neurobiological processes and disease mechanisms impacting men and women in space.