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Abstract
The space radiation environment consists of multiple species of charged particles, including 28Si ions, that may impact brain function during and following missions. To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. The plasma of the mice was collected for analysis of miRNA levels. Select pertinent brain regions were dissected for lipidomic analyses and analyses of levels of select biomarkers shown to be sensitive to effects of space radiation in previous studies. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Levels of the dendritic marker MAP2 in the cortex were higher in irradiated than sham-irradiated mice at middle age, which might be part of a compensatory response. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation could be used for the development of biomarker of the space radiation response.
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1 Oregon Health & Science University-Portland State University School of Public Health, Knight Cancer Institute Biostatistics Shared Resource, and the Knight Cardiovascular Institute, OR Health & Science University, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690)
2 University of Texas Medical Branch Cancer Center, Department of Biochemistry and Molecular Biology; Radiation Oncology, Pharmacology and Toxicology, Mitchell Center for Neurodegenerative Diseases, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964)
3 L470, Oregon Health & Science University, Department of Behavioral Neuroscience, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690)
4 University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
5 Lerner Research Institute, Cleveland Clinic Lerner College of Medicine US, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725)
6 Lerner Research Institute, Cleveland Clinic Lerner College of Medicine US, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725); Genomic Medicine Institute, Case Western Reserve University US., Department of Molecular Medicine, School of Medicine, GU Malignancies Program, Case Comprehensive Cancer Center, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847)
7 Colorado State University, Department of Environmental and Radiological Health Sciences, Fort Collins, USA (GRID:grid.47894.36) (ISNI:0000 0004 1936 8083)
8 University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121); University of Texas Southwestern Medical Center, Simmons Comprehensive Cancer Center, Dallas, USA (GRID:grid.267313.2) (ISNI:0000 0000 9482 7121)
9 L470, Oregon Health & Science University, Department of Behavioral Neuroscience, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690); Oregon Health & Science University, Division of Neuroscience ONPRC, Departments of Neurology, Psychiatry, and Radiation Medicine, Portland, USA (GRID:grid.5288.7) (ISNI:0000 0000 9758 5690)