Laiakis Evagelia C, Pinheiro Maisa, Nguyen Tin, Nguyen Hung, Beheshti Afshin, Dutta Sucharita M, Russell William K, Emmett Mark R, Britten Richard A
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United States.
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, United States.
Front Physiol. 2022 Aug 26;13:971282. doi: 10.3389/fphys.2022.971282. eCollection 2022.
NASA's planned mission to Mars will result in astronauts being exposed to ∼350 mSv/yr of Galactic Cosmic Radiation (GCR). A growing body of data from ground-based experiments indicates that exposure to space radiation doses (approximating those that astronauts will be exposed to on a mission to Mars) impairs a variety of cognitive processes, including cognitive flexibility tasks. Some studies report that 33% of individuals may experience severe cognitive impairment. Translating the results from ground-based rodent studies into tangible risk estimates for astronauts is an enormous challenge, but it would be germane for NASA to use the vast body of data from the rodent studies to start developing appropriate countermeasures, in the expectation that some level of space radiation (SR) -induced cognitive impairment could occur in astronauts. While some targeted studies have reported radiation-induced changes in the neurotransmission properties and/or increased neuroinflammation within space radiation exposed brains, there remains little information that can be used to start the development of a mechanism-based countermeasure strategy. In this study, we have employed a robust label-free mass spectrometry (MS) -based untargeted quantitative proteomic profiling approach to characterize the composition of the medial prefrontal cortex (mPFC) proteome in rats that have been exposed to 15 cGy of 600 MeV/nSi ions. A variety of analytical techniques were used to mine the generated expression data, which in such studies is typically hampered by low and variable sample size. We have identified several pathways and proteins whose expression alters as a result of space radiation exposure, including decreased mitochondrial function, and a further subset of proteins differs in rats that have a high level of cognitive performance after SR exposure in comparison with those that have low performance levels. While this study has provided further insight into how SR impacts upon neurophysiology, and what adaptive responses can be invoked to prevent the emergence of SR-induced cognitive impairment, the main objective of this paper is to outline strategies that can be used by others to analyze sub-optimal data sets and to identify new information.
美国国家航空航天局（NASA）计划执行的火星任务将使宇航员每年受到约350毫希沃特的银河宇宙辐射（GCR）。来自地面实验的越来越多的数据表明，暴露于太空辐射剂量（接近宇航员执行火星任务时将受到的剂量）会损害多种认知过程，包括认知灵活性任务。一些研究报告称，33%的个体可能会经历严重的认知障碍。将地面啮齿动物研究的结果转化为对宇航员切实可行的风险评估是一项巨大的挑战，但NASA利用啮齿动物研究的大量数据开始制定适当的对策是恰当的，因为预计宇航员可能会出现一定程度的太空辐射（SR）诱发的认知障碍。虽然一些针对性研究报告了太空辐射暴露大脑中神经传递特性的辐射诱导变化和/或神经炎症增加，但几乎没有可用于启动基于机制的对策策略开发的信息。在本研究中，我们采用了一种基于无标记质谱（MS）的强大非靶向定量蛋白质组学分析方法，来表征暴露于15厘戈瑞的600兆电子伏/纳米硅离子的大鼠内侧前额叶皮质（mPFC）蛋白质组的组成。我们使用了多种分析技术来挖掘生成的表达数据，在这类研究中，样本量低且变化通常会阻碍此类分析。我们已经确定了几种因太空辐射暴露而表达发生改变的途径和蛋白质，包括线粒体功能下降，并且与认知表现水平低的大鼠相比，在太空辐射暴露后认知表现水平高的大鼠中，还有一部分蛋白质存在差异。虽然这项研究进一步深入了解了太空辐射如何影响神经生理学，以及可以调用哪些适应性反应来防止太空辐射诱发的认知障碍的出现，但本文的主要目的是概述其他人可用于分析次优数据集并识别新信息的策略。
