Effects of Proton Radiation on Behavior in a Mouse Model of Alzheimer’s Disease

Abstract

Astronauts venturing outside Earth’s magnetosphere risk exposure to charged particle radiation that has been shown to cause neurological deficits in rodents via oxidative stress, neuroinflammation, altered neurogenesis, and synaptic changes. Since these responses are similar to those observed in age-related neurodegenerative diseases, we hypothesized that individuals with a propensity toward developing Alzheimer’s disease (AD) would be more adversely affected by such exposure. To test this hypothesis, we exposed young double transgenic APP/PSEN1 mice (a commercially available strain engineered to develop AD-like neuropathology) and their wild-type (non-transgenic) counterparts to low doses of 150 MeV proton particle radiation and assessed the effects on hippocampus-dependent behaviors. Spatial learning ability, a sensitive behavioral marker of hippocampal damage, was assessed using the water maze and Barnes maze 3 and 6 months after irradiation. Transgenic mice performed worse than wild-type mice on both behavioral measures, and wild-type mice exposed to 0.5 Gy performed worse than the 0 Gy wild-type mice at 6 months post-irradiation. However, radiation doses up to 1 Gy had no effect on transgenic spatial learning performance. These findings suggest that low doses of proton radiation cause deficits in normal individuals, but may not exacerbate or accelerate learning and memory deficits in individuals predisposed toward age-related neurological disease