Raber Jacob, Holden Sarah, Kessler Kat, Glaeser Breanna, McQuesten Chloe, Chaudhari Mitali, Stenzel Fiona, Lenarczyk Marek, Leonard Scott Willem, Morré Jeffrey, Choi Jaewoo, Kronenberg Amy, Borg Alexander, Kwok Andy, Stevens Jan Frederik, Olsen Christopher, Willey Jeffrey S, Bobe Gerd, Minnier Jessica, Baker John E
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States.
Departments of Neurology, and Radiation Medicine, Division of Neuroscience ONPRC, Oregon Health & Science University, Portland, OR, United States.
Front Physiol. 2024 Jan 8;14:1316186. doi: 10.3389/fphys.2023.1316186. eCollection 2023.
The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures. A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses. The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures. These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.
宇航员在太空任务期间所经历的空间环境包含多种环境挑战，其中包括微重力。在本研究中，我们评估了雄性Fisher大鼠在假照射或全身光子照射2个月后的行为和认知表现，照射条件为有无模拟微重力。我们分析了假照射或全身照射9个月后采集的血浆，以确定代谢途径的明显变化，并确定代谢指标的变化是否与特定的行为和认知指标相关。总共344只雄性Fisher大鼠在有无通过后肢卸载（HU）实现的模拟失重情况下接受了光子（6 MeV；3、8或10 Gy）照射。为了确定光子辐射暴露或HU条件下行为或认知表现的潜在血浆生物标志物，我们进行了回归分析。HU对旷场活动水平、高架十字迷宫焦虑测量以及M&M消耗试验中快感缺失的行为影响比光子照射更为明显。在接受3 Gy照射的动物中，苯丙氨酸、酪氨酸和色氨酸代谢以及苯丙氨酸代谢和生物合成在光子照射和HU后显示出非常强烈的途径变化。在此，101种血浆代谢物中的29种与13种行为指标中的1种相关。在没有HU的情况下，22种代谢物与行为和认知指标相关。在假照射或接受8 Gy照射的HU动物中，一种代谢物与行为和认知指标相关。在接受3 Gy照射的HU动物中，六种代谢物与行为和认知指标相关。这些数据表明，在面临HU和辐射暴露等环境挑战后，有可能开发出行为和认知表现的稳定血浆生物标志物。
