High-Energy, Whole-Body Proton Irradiation Differentially Alters Long-Term Brain Pathology and Behavior Dependent on Sex and Alzheimer’s Disease Mutations
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ijms-24-03615.pdf
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Author(s)
Hinshaw, Robert G.
Schroeder, Maren K.
Ciola, Jason
Varma, Curran
Colletti, Brianna
Liu, Bin
Liu, Grace Geyu
Shi, Qiaoqiao
Williams, Jacqueline P.
O’Banion, M. Kerry
Date Issued
February 10, 2023
Publisher
Multidisciplinary Digital Publishing Institute
Citation
International Journal of Molecular Sciences 24 (4): 3615 (2023)
Version
Final published version
Abstract
Whole-body exposure to high-energy particle radiation remains an unmitigated hazard to human health in space. Ongoing experiments at the NASA Space Radiation Laboratory and elsewhere repeatedly show persistent changes in brain function long after exposure to simulations of this unique radiation environment, although, as is also the case with proton radiotherapy sequelae, how this occurs and especially how it interacts with common comorbidities is not well-understood. Here, we report modest differential changes in behavior and brain pathology between male and female Alzheimer’s-like and wildtype littermate mice 7–8 months after exposure to 0, 0.5, or 2 Gy of 1 GeV proton radiation. The mice were examined with a battery of behavior tests and assayed for amyloid beta pathology, synaptic markers, microbleeds, microglial reactivity, and plasma cytokines. In general, the Alzheimer’s model mice were more prone than their wildtype littermates to radiation-induced behavior changes, and hippocampal staining for amyloid beta pathology and microglial activation in these mice revealed a dose-dependent reduction in males but not in females. In summary, radiation-induced, long-term changes in behavior and pathology, although modest, appear specific to both sex and the underlying disease state.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.3390/ijms24043615
