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Long-Term Sex- and Genotype-Specific Effects of 56Fe Irradiation on Wild-Type and APPswe/PS1dE9 Transgenic Mice
Name
ijms-22-13305.pdf
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2.93 MB
Format
Adobe PDF
Checksum (MD5)
86218204a8488d2c89a2495b1e08584d
Author(s)
Schroeder, Maren K.
Liu, Bin
Hinshaw, Robert G.
Park, Mi-Ae
Wang, Shuyan
Dubey, Shipra
Liu, Grace Geyu
Shi, Qiaoqiao
Holton, Peter
Reiser, Vladimir
Date Issued
December 10, 2021
Publisher
Multidisciplinary Digital Publishing Institute
Citation
International Journal of Molecular Sciences 22 (24): 13305 (2021)
Version
Final published version
Abstract
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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DOI of Published Version
http://dx.doi.org/10.3390/ijms222413305
