Neuroinflammatory Signaling and Immune Cell Infiltration Differ in Brains of Rats Exposed to Space Radiation and Social Isolation.

Astronauts on the proposed Mars missions will be exposed to extended periods of social isolation (SI) and space radiation (SR). SI and SR-induced immune dysregulation can result in persistent neuroinflammation and neuronal damage which could negatively impact an astronaut's health and ability to maintain adequate levels of performance. The synergistic effects of combined SI and SR on immune system functionality and the brain remain unknown. Determining how single and combined inflight stressors modulate the immune system is crucial for fully understanding pathways impacting astronaut health and performance. We used ground-based analogs of SI and SR in rodent models to investigate how SI and SR, and their combination (dual flight stressors (DFS)), impact immune cell recruitment into the brain and alter gene expression related to immune signaling and neuroinflammation. We also assessed whether putative phenotypic differences in stress resilience and vulnerability were reflected in neuroinflammatory-related gene expression. SI rats exhibited differences in neuroinflammatory signaling but no differences in infiltrating cells compared to Controls. SR rats exhibited up-regulated gene expression related to cytokine signaling and immune cell recruitment and unexpectedly depleted infiltrating immune cells. Many deficits related to the immune response in the SR animals were attenuated by dual exposure to SI. These data demonstrate significant differences in the effects of spaceflight stressors on immune function and how they may vary with individual stress resilience and vulnerability.