Investigation of neuroprotection by NAD+ in response to deep space radiation
Shelerud, Lukas M.
MetadataShow full item record
BACKGROUND: As space programs such as NASA prepare for interplanetary missions to Mars, the potential hazards of long-term space travel are being increasingly considered. Of these hazards, astronaut exposure to galactic cosmic radiation (GCR) is of specific concern. Despite increased efforts to study the consequences of deep space radiation exposure, studies have been inconsistent in their dosage and types of radiation used. This study marks the first to use a simulated form of GCR, accurately representing the dosage and full spectrum of ions astronauts would encounter on an extended journey to Mars. The disruption of cognition and behavior by radiation has been a hallmark of previous investigations, however, it is unknown whether accurate full-spectrum GCR causes similar impairment. Additionally, reports exploring the efficacy of radioprotectant drugs are lacking despite their potential utility in deep space travel. Nicotinamide Mononucleate, an NAD+ precursor, shows promise for radioprotection, as its roles in promoting DNA repair and longevity pathways in mice are well established. OBJECTIVE: To define behavioral responses to accurate full-spectrum Galactic Cosmic Radiation (GCR) in mice and test the neuroprotective potential of an NAD+ booster, nicotinamide mononucleotide (NMN). METHODS: Male C57BL/6 mice (n=48) began NMN treatment (600 mg/kg daily) and GCR radiation exposure at six months of age. Mice (n=24) were exposed to GCR for 24 total days for a total dose of ~49.92 cGy before being shipped to Harvard Medical School for analysis. Between nine and 11.5 months of age, all mice underwent a series of behavioral assays. Learning and memory behaviors were assessed using the Barnes Maze test and measured by comparing time spent at the target hole and target quadrant. Anxiety and motility were assessed using the Open Field test and measured by comparing the % time spent in the center of the maze and total distances traveled. Dominance and aggression were assessed using the Tube Dominance test and measured in total number of bouts won by each mouse. RESULTS: Mice from all four groups showed no difference in percentage of time spent at the target hole or in percentage of time spent within the target quadrant, indicating that mouse learning and memory were unaffected by chronic GCR and NMN treatment. Mice from all four groups showed no difference in percentage of time spent in the center of the maze, or in total distance traveled, suggesting that mouse anxiety and motility were unaffected by chronic GCR and NMN treatment. Irradiated mice were found to be significantly more dominant than non-irradiated mice as determined by the Tube Dominance test. When comparing irradiated mice +/- NMN, it was found that NMN treated mice scored 90.9% lower in dominance. CONCLUSIONS: Behavioral results indicate very limited potential for neurological impairment by accurate, full-spectrum GCR in mice, however, further research is needed to confirm this. Mouse dominance behavior was found to be affected by GCR, suggesting future behavioral studies should include dominance and aggression analyses. NMN shows potential as a novel radioprotective agent that should be further investigated.