Fractionated Proton Irradiation Does Not Impair Hippocampal-Dependent Short-Term or Spatial Memory in Female Mice

The environment outside the Earth's protective magnetosphere is a much more threatening and complex space environment. The dominant causes for radiation exposure, solar particle events and galactic cosmic rays, contain high-energy protons. In space, astronauts need healthy and highly functioning cognitive abilities, of which the hippocampus plays a key role. Therefore, understanding the effects of ¹H exposure on hippocampal-dependent cognition is vital for developing mitigative strategies and protective countermeasures for future missions. To investigate these effects, we subjected 6-month-old female CD1 mice to 0.75 Gy fractionated ¹H (250 MeV) whole-body irradiation at the NASA Space Radiation Laboratory. The cognitive performance of the mice was tested 3 months after irradiation using Y-maze and Morris water maze tests. Both sham-irradiated and ¹H-irradiated mice significantly preferred exploration of the novel arm compared to the familiar and start arms, indicating intact spatial and short-term memory. Both groups statistically spent more time in the target quadrant, indicating spatial memory retention. There were no significant differences in neurogenic and gliogenic cell counts after irradiation. In addition, proteomic analysis revealed no significant upregulation or downregulation of proteins related to behavior, neurological disease, or neural morphology. Our data suggests ¹H exposure does not impair hippocampal-dependent spatial or short-term memory in female mice.