Sudevan Surabhi, Muto Kasumi, Higashitani Nahoko, Hashizume Toko, Higashibata Akira, Ellwood Rebecca A, Deane Colleen S, Rahman Mizanur, Vanapalli Siva A, Etheridge Timothy, Szewczyk Nathaniel J, Higashitani Atsushi
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan.
Medical Research Council (MRC) Versus Arthritis Centre for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, UK.
iScience. 2022 Jan 11;25(2):103762. doi: 10.1016/j.isci.2022.103762. eCollection 2022 Feb 18.
Progressive neuromuscular decline in microgravity is a prominent health concern preventing interplanetary human habitation. We establish functional dopamine-mediated impairments as a consistent feature across multiple spaceflight exposures and during simulated microgravity in . Animals grown continuously in these conditions display reduced movement and body length. Loss of mechanical contact stimuli in microgravity elicits decreased endogenous dopamine and (catechol-O-methyl transferase) expression levels. The application of exogenous dopamine reverses the movement and body length defects caused by simulated microgravity. In addition, increased physical contact made and dopamine levels rise. It also increased muscular cytoplasmic Ca firing. In (D2-like receptor) mutants, neither decrease in movement nor in body length were observed during simulated microgravity growth. These results strongly suggest that targeting the dopamine system through manipulation of the external environment (contact stimuli) prevents muscular changes and is a realistic and viable treatment strategy to promote safe human deep-space travel.
微重力环境下进行性神经肌肉衰退是阻碍星际人类居住的一个突出健康问题。我们发现功能性多巴胺介导的损伤是多次太空飞行暴露以及模拟微重力期间的一个一致特征。在这些条件下持续生长的动物表现出运动减少和体长缩短。微重力环境下机械接触刺激的丧失引发内源性多巴胺和儿茶酚-O-甲基转移酶(catechol-O-methyl transferase)表达水平降低。外源性多巴胺的应用可逆转模拟微重力导致的运动和体长缺陷。此外,增加身体接触会使多巴胺水平升高,还会增加肌肉细胞质钙放电。在D2样受体(D2-like receptor)突变体中,模拟微重力生长期间未观察到运动或体长减少。这些结果有力地表明,通过操纵外部环境(接触刺激)来靶向多巴胺系统可预防肌肉变化,是促进人类安全深空旅行的一种现实可行的治疗策略。