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, OR, 97239, USA.
Department of Biochemistry and Molecular Biology; Radiation Oncology, Pharmacology and Toxicology, Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch Cancer Center, Galveston, TX, 77555, USA.
Sci Rep. 2021 Jul 21;11(1):14899. doi: 10.1038/s41598-021-93869-3.
The space radiation environment consists of multiple species of charged particles, including Si 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 Si 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 Si 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 Si ion irradiation could be used for the development of biomarker of the space radiation response.
空间辐射环境由多种带电粒子组成,包括硅离子,这些粒子可能会在任务期间和之后影响大脑功能。为了开发空间辐射反应的生物标志物,BALB/c 和 C3H 雌性和雄性小鼠及其 F2 杂交后代接受了硅离子(350 MeV/n,0.2 Gy)辐射,并在辐射后 1、6 和 12 个月进行了行为和认知表现测试。收集小鼠的血浆进行 miRNA 水平分析。选择相关的脑区进行脂质组学分析,并分析以前的研究表明对空间辐射敏感的选定生物标志物的水平。在接受硅离子辐射后,特定脑区的脂质、血浆 miRNA 与认知测量和行为之间存在关联。在假照射和照射的小鼠中,在三个时间点发现不同但重叠的血浆 miRNA 与认知测量和行为相关。辐射条件揭示了与神经退行性疾病和癌症相关的途径。在中年时,皮质中树突标记物 MAP2 的水平在照射组比假照射组高,这可能是一种代偿反应。在 miRNA 中以解剖学上不同的方式与 CD68 也存在关系,表明不同的 miRNA 以不同的方式调节不同脑区的神经炎症。硅离子辐射后选定脑区的脂质、血浆 miRNA 与行为和认知测量之间的关联可用于开发空间辐射反应的生物标志物。