Plasma and Brain Cytokine Responses to Single and Combinatorial Spaceflight Stressors in Male and Female Mice
Spaceflight involves exposure to multiple environmental stressors, including Ionizing Radiation (IR), microgravity, and social isolation. We hypothesize that spaceflight stressors combine synergistically to trigger an oxidative stress response that, in turn, alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Here, we report plasma and brain cytokine findings from two studies of crew age-matched (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim at the NASA Space Radiation Laboratory (NSRL). In Study 1, mice were exposed to 0, 5, 15, or 50cGy 5-ion GCRsim. Immune and brain measures were acquired either at ‘Acute’ (within 3 days post-irradiation; IR), ‘Intermediate’ (IR+14 days) or ‘Delayed’ (IR+125 days) timepoints. In Study 2, mice were exposed singly and in combination to 15cGy 5-ion GCRsim, simulated microgravity via continuous head-down tilt/hindlimb unloading (HU), and social isolation. Plasma and brain cytokine cytokine profiling revealed sex-specific as well as sex-common responses. Notably, plasma granulocyte colony stimulating factor (GCSF) levels showed significant regulation compared to a single stressor alone, suggesting a potential biomarker responder. Increased GCSF was correlated with corresponding increased blood neutrophil populations. Futhermore, our study provides evidence for robust effects of HU relative to IR alone. This project addresses NASA’s efforts to characterize risks in both women and men in anticipation of future space missions beyond low earth orbit (BLEO). Ensuring crew health and performance during extended transits to the moon and beyond necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.