Effects of a 33-sequential beam galactic cosmic ray analog on male mouse behavior and evaluation of CDDO-EA as a radiation countermeasure

In long-term spaceflight, astronauts will face unique cognitive loads and social challenges which will be complicated by communication delays with Earth. It is important to understand the central nervous system (CNS) effects of deep spaceflight and the associated unavoidable exposure to galactic cosmic radiation (GCR). Rodent studies show single- or simple-particle combination exposure alters CNS endpoints, including hippocampal-dependent behavior. An even better Earth-based simulation of GCR is now available, including 33-beam GCR (33-GCR) exposure. However, the effect of whole-body 33-GCR exposure on rodent behavior is unknown, and no 33-GCR CNS countermeasures have been tested. Here astronaut-age-equivalent (6mo-old) C57BL/6J male mice were exposed to a 33-GCR (75cGy, a Mars mission dose). Pre-/during/post-Sham or 33-GCR exposure, mice were given a diet containing a "vehicle" formulation or the antioxidant/anti-inflammatory compound CDDO-EA as a potential countermeasure. Behavioral testing beginning 4mo post-irradiation suggested radiation and diet did not affect measures of exploration/anxiety-like behaviors (open field, elevated plus maze) or recognition of a novel object. However, in 3-Chamber Social Interaction (3-CSI), CDDO-EA/33-GCR mice failed to spend more time exploring a holder containing a stranger mouse vs. nothing, suggesting sociability deficits, and Vehicle/33-GCR and CDDO-EA/Sham mice failed to discriminate between a stranger vs. familiar mouse, suggesting social memory deficits. CDDO-EA given pre-/during/post-irradiation did not attenuate the 33-GCR-induced social memory deficits. Future elucidation of the mechanisms underlying 33-GCR-induced social memory deficits will improve risk analysis for astronauts which may in-turn improve countermeasures.