The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures (Elevated Plus Maze, Novel Object Recognition, Open Field, Radial Arm Water Maze, and Three Chamber Social Isolation/Interaction)

Exposure to galactic cosmic radiation (GCR) is a major obstacle for deep space travel. Using multivariate principal components analysis, we found sex dimorphic responses in mice exposed to accelerated charged particles to simulate GCR (GCRsim); males displayed impaired spatial learning, whereas females did not.

Mechanistically, these GCRsim induced learning impairments corresponded with chronic microglia activation and synaptic alterations in the hippocampus. Temporary microglia depletion shortly after GCRsim exposure mitigated GCRsim induced deficits measured months after the radiation exposure. Furthermore, blood monocyte levels measured early after GCRsim exposure were predictive of the late learning deficits and microglia activation measured in the male mice.