ApoE isoform modulates effects of cranial ⁵⁶Fe irradiation on spatial learning and memory in the water maze

Apolipoprotein E, which plays an important role in lipid transport and metabolism and neuronal repair, might modulate the CNS risk following ⁵⁶Fe irradiation exposure during space missions. In this study, we investigated this risk by behavioral and cognitive testing male E2, E3, and E4 mice 3 months following cranial ⁵⁶Fe irradiation. In the open field, mice irradiated with 2Gy showed higher activity levels than sham-irradiated mice or mice irradiated with 1Gy. In addition, E2 mice showed higher activity and lower measures of anxiety than E3 and E4 mice in the open field and elevated zero maze. During hidden platform training, sham-irradiated mice showed most robust learning, 1Gy irradiated mice reduced learning, and 2Gy irradiated mice no improvement over the four sessions. In the water maze probe trials, sham-irradiated E2, E3, and E4 mice and E2 and E4 mice irradiated with 1Gy showed spatial memory retention, but E3 mice irradiated with 1Gy, and E2, E3, and E4 mice irradiated with 2Gy did not. Thus, cranial ⁵⁶Fe irradiation increases activity levels in the open field and impairs spatial learning and memory in the water maze. E3 mice are more susceptible than E2 or E4 mice to impairments in spatial memory retention in the water maze, indicating that apoE isoform modulates the CNS risk following space missions.