Effectiveness of artificial gravity to maintain muscle strength and neuromuscular interaction during 60 days of bedrest

以肌肉无力和肌肉量减少为特征的神经肌肉系统失调，是在长期空间飞行任务期间和卧床休息（如病人）时观察到的对失重作出反应的主要生理变化之一。肌肉萎缩和肌肉激活能力受损可能是废用诱导的神经肌肉接头（NMJ）重塑的结果。NMJ的这种适应可能会损害突触后信号传导和兴奋-收缩偶联。神经营养素和神经营养因子对NMJ的完整性起着重要作用。神经肌肉疾病和衰老中的线粒体功能障碍，与肌肉萎缩相关的病症，有助于NMJ完整性的丧失。此外，功能性运动单位的丧失可能导致肌肉功能的丧失，并可能由脊髓上活动模式的改变引起。上述观察结果表明，神经肌肉相互作用是肌肉质量和功能损失的有效对策的关键目标。在过去的几十年里，许多研究已经表明各种对策可以有效预防微重力引起的肌肉萎缩。目前，国际空间站（ISS）上的宇航员每天花费2.5小时的宝贵时间进行锻炼，以防止肌肉骨骼和心血管失调。为了缩短日常训练时间，提高训练效果，需要探索未来长期任务的替代对策。短臂离心机产生的人工重力是一种很有前途的新选择，它模仿了我们自然的1-G环境，可以有效地保护肌肉骨骼系统。由于测试人体离心作用的研究的第一批数据很有希望，欧洲航天局（欧空局）目前正在与美国航天局合作进行一系列床上用品研究，以研究对人体的影响及其作为对策的详细实施情况。我与包括曼彻斯特城市大学的Hans Degens教授在内的五位国际同事一起，成功地向欧空局提出了一个项目，该项目将在2019年将我们的实验整合到一项为期60天的卧床研究中。我们的实验包括1.肌肉组织和血液样品的神经营养因子和反映NMJ状态的NMJ分解产物的分子分析，2.功能运动单位数量和H反射兴奋性的测量，3。这些因素与肌肉功能和分子形态学的相关性。分析人类离心能在多大程度上阻止这些变化。

Deconditioning of the neuro-muscular system, characterised by muscle weakness and a reduction in muscle mass, is one of the major physiological changes observed in response to weightlessness during long-term space missions and in bedrest (e.g. in patients). Atrophy and impaired muscle activation capacity may be the consequence of disuse-induced remodelling of the neuro-muscular junctions (NMJ). Such adaptations of the NMJ may impair post-synaptic signaling and excitation-contraction coupling. Neurotrophins and neurotrophic factors play an important role for the integrity of the NMJ. Mitochondrial dysfunction in neuromuscular diseases and ageing, conditions associated with muscle wasting, contributes to loss of NMJ integrity. In addition, a loss of functional motor units might contribute to losses in muscle function and might result from alterations in supra-spinal activity patterns. The above observations indicate that neuromuscular interaction is a key target for effective countermeasures of loss of muscle mass and function. In the last decades, many studies have shown the efficacy of various countermeasures to prevent microgravity-induced muscle wasting. Astronauts on the International Space Station (ISS) currently spend 2.5 h per day of valuable crew time to exercise to prevent musculoskeletal and cardiovascular deconditioning. To shorten daily exercise time and improve training efficacy, alternative countermeasures need to be explored for future long-term missions. Artificial gravity generated by short-arm centrifuges is a promising new option that mimics our natural 1-G environment and may efficiently protect the musculoskeletal system. As first data from studies testing human centrifugation are promising, the European Space Agency (ESA) currently conducts a series of bedrest-studies in cooperation with NASA to study the effects on the human body and its implementation as a countermeasure in detail. Together with a group of five international colleagues including Prof. Hans Degens of Manchester Metropolitan University, I have successfully proposed a project to ESA that will integrate our experiments into a 60-days bedrest study in 2019. Our experiments include 1. molecular analyses of muscle tissue and blood samples for neurotropic factors and breakdown products of the NMJ that reflect the state of the NMJ, 2. Measurements of the number of functional motor units and excitability of the H-reflex, 3. Correlation of these factors with muscle function and molecular morphology and 4. The analysis in how far human centrifugation can stop these changes.