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

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

doi:10.3390/ijms222413305

Maren K Schroeder, M Kerry O’Banion + Show 15 more

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https://doi.org/10.3390/ijms222413305

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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.

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The National Aeronautics and Space Administration (NASA) is preparing for lunar base habitation and multi-year, crewed missions to Mars
Irradiation with 56Fe did not affect body weight, all groups of mice were significantly heavier at 12 months of age than they were at 4 months due to aging (Supplementary Figure S1D)
There were no differences between groups on grip strength (Supplementary Figure S1F), though there was a trend towards sham-irradiated WT females having higher latencies to fall in the wire hanging test than sham-irradiated amyloid precursor protein (APP)/presenilin 1 (PS1) females, suggesting better endurance in WT female mice (Supplementary Figure S1G)

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The National Aeronautics and Space Administration (NASA) is preparing for lunar base habitation and multi-year, crewed missions to Mars. HZE particles are known to affect a variety of biological systems; previous research in rodents suggests that several months following low-dose (less than 1 Gy) 56Fe exposure, there is an increase in fibrosisassociated genes and hypermethylation in the lung [3] as well as aberrant blood chemistry associated with liver and kidney function [4]. While central nervous system (CNS) tissues have traditionally been considered radioresistant, increasing evidence suggests that low doses of HZE particle radiation pose a threat to these tissues as well. The potential long-term effects of HZE particle exposure on the CNS are of high importance to space medicine research

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