Oxidative Stress and Neuroconsequences of the Spaceflight Environment –A 5-ion GCRsim Dose-response Study

The overall scope of this project is to test the hypothesis that Ionizing Radiation (IR), microgravity
and social isolation combine synergistically to trigger an oxidative stress response that alters
immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance.
Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR
Simulation’ exposure for immune, brain and performance responses in crew age-matched adult
male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly
and in combination with simulated microgravity and social isolation, on immune, brain and
performance responses in crew age-matched male and female mice mimicking deep space
missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide
(NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we
exposed mature (23-24-week-old) male and female mice to simulated 5-Ion GCR (either 0, 5, 15,
or 50cGy) at the NASA Space Radiation Laboratory (NSRL). Across ‘Acute’ (IR+72hrs and
IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) phases of the 6-month-long study, we assessed
immune, neural, and functional (sensorimotor/behavioral/cognitive) responses anticipated during
a transit to Mars. This presentation will report on dose-response curves for 5-ion GCRsim related
to potential biomarkers; structural/functional changes in the immune and nervous systems; and
behavioral/cognitive performance deficits. This project addresses NASA’s efforts to characterize
risks and identify appropriate countermeasures in anticipation of future deep space missions.
Ensuring crew health and performance during extended transits necessitates that sensorimotor and
cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.