Long-Term, Sex-Specific Effects of GCRsim and Gamma Irradiation on the Brains, Hearts, and Kidneys of Mice with Alzheimer's Disease Mutations.

Autor: Varma C; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA., Schroeder MK; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA., Price BR; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA., Khan KA; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA., Curty da Costa E; Department of Regenerative Medicine Research, Texas Heart Institute, Houston, TX 77030, USA., Hochman-Mendez C; Department of Regenerative Medicine Research, Texas Heart Institute, Houston, TX 77030, USA., Caldarone BJ; Mouse Behavioral Core, Harvard Medical School, Boston, MA 02115, USA., Lemere CA; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Aug 16; Vol. 25 (16). Date of Electronic Publication: 2024 Aug 16.
DOI: 10.3390/ijms25168948
Abstrakt: Understanding the hazards of space radiation is imperative as astronauts begin voyaging on missions with increasing distances from Earth's protective shield. Previous studies investigating the acute or long-term effects of specific ions comprising space radiation have revealed threats to organs generally considered radioresistant, like the brain, and have shown males to be more vulnerable than their female counterparts. However, astronauts will be exposed to a combination of ions that may result in additive effects differing from those of any one particle species. To better understand this nuance, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like mice with 0, 0.5, or 0.75 Gy galactic cosmic ray simulation (GCRsim) or 0, 0.75, or 2 Gy gamma radiation (wild-type only). At 11 months, mice underwent brain and heart MRIs or behavioral tests, after which they were euthanized to assess amyloid-beta pathology, heart and kidney gene expression and fibrosis, and plasma cytokines. Although there were no changes in amyloid-beta pathology, we observed many differences in brain MRIs and behavior, including opposite effects of GCRsim on motor coordination in male and female transgenic mice. Additionally, several genes demonstrated persistent changes in the heart and kidney. Overall, we found sex- and genotype-specific, long-term effects of GCRsim and gamma radiation on the brain, heart, and kidney.
Databáze: MEDLINE
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