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Long-Term Sex- and Genotype-Specific Effects of 56Fe Irradiation on Wild-Type and APPswe/PS1dE9 Transgenic Mice

2021; Multidisciplinary Digital Publishing Institute; Volume: 22; Issue: 24 Linguagem: Inglês

10.3390/ijms222413305

1661-6596

Maren K. Schroeder, Bin Liu, Robert G. Hinshaw, Mi‐Ae Park, Shuyan Wang, Shipra Dubey, Grace Geyu Liu, Qiaoqiao Shi, Peter Holton, Vladimı́r Reiser, Paul A. Jones, William Trigg, Marcelo F. Di Carli, Barbara J. Caldarone, Jacqueline P. Williams, M. Kerry O’Banion, Cynthia A. Lemere,

Mitochondrial Function and Pathology

Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer's disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of 56Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56Fe irradiation worsened amyloid-beta (Aβ) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral Aβ and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation.