Reduced set-shifting processing speed in male rats following low dose (10 cGy) proton exposure

Space radiation (SR) exposure poses significant biomedical risks, including effects on the central nervous system (CNS). These risks are particularly relevant to cognitive function during long-duration space missions. One critical cognitive skill is decision-making, which requires attentional set-shifting (ATSET)-the ability to quickly assess problems, evaluate options, and select the best actions. Previous studies have shown that exposure to <10 cGy of SR ions impairs ATSET performance in animal models. However, the impact of low LET (< 1 keV/μm) protons, which significantly contribute to the total radiation flux astronauts encounter within spacecraft, on ATSET performance is unknown. To address this gap, we evaluated the effects of cranial irradiation with 10 cGy of 100 MeV/n protons (LET = 0.732 keV/μm) on ATSET performance in male Sprague-Dawley rats. We also investigated whether concurrent exposure to variable gravity (hypergravity step-up, step down, purported to have the same effect as exposure to microgravity (another major spaceflight stressor) exacerbated SR-induced cognitive deficits. Our findings indicate that proton exposure alone significantly impaired ATSET performance, as evidenced by decreased processing speed while performing compound discrimination reversal and extra-dimensional shifting. Notably, no additive or synergistic effects were observed when hypergravity was combined with proton exposure. The impact that low-dose proton exposure has on CNS functionality, particularly in reducing processing speed during complex tasks, warrant further investigation. If similar cognitive deficits were to occur in astronauts exposed to galactic cosmic rays, mission success and safety could be significantly compromised.