Long-term sex-and genotype-specific effects of56 fe irradiation on wild-type and appswe/ps1de9 transgenic mice

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

Research output: Contribution to journalArticlepeer-review

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 that56 Fe 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 of56 Fe 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 of56 Fe 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.56 Fe 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.

Original languageEnglish (US)
Article number13305
JournalInternational journal of molecular sciences
Volume22
Issue number24
DOIs
StatePublished - Dec 1 2021
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Fe radiation
  • Sex differences

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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