TY - JOUR
T1 - Long-term sex-and genotype-specific effects of56 fe irradiation on wild-type and appswe/ps1de9 transgenic mice
AU - Schroeder, Maren K.
AU - Liu, Bin
AU - Hinshaw, Robert G.
AU - Park, Mi Ae
AU - Wang, Shuyan
AU - Dubey, Shipra
AU - Liu, Grace Geyu
AU - Shi, Qiaoqiao
AU - Holton, Peter
AU - Reiser, Vladimir
AU - Jones, Paul A.
AU - Trigg, William
AU - Di Carli, Marcelo F.
AU - Caldarone, Barbara J.
AU - Williams, Jacqueline P.
AU - O’banion, M. Kerry
AU - Lemere, Cynthia A.
N1 - Funding Information:
Funding: This research was funded by grants from the National Aeronautic and Space Administration (NASA): NNX14AI07G and 80NSSC18K0810 (both to CAL).
Funding Information:
Acknowledgments: We are grateful to NASA for funding this project and to General Electric (GE) for providing the 18F-GE180 TSPO PET tracer as a gift-in-kind. We also thank Adam Rusek, Peter Guida, Paula Bennett, and Deborah Snyder at NSRL for their help with the irradiation process, as well as Kevin Le, Anthony Belanger, Jeff Frost, Lee Trojanczyk, and Paul Lorello for their expert technical assistance.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Fe radiation
KW - Sex differences
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U2 - 10.3390/ijms222413305
DO - 10.3390/ijms222413305
M3 - Article
C2 - 34948098
AN - SCOPUS:85120778861
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 24
M1 - 13305
ER -