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

神经肌肉系统的去条件化，以肌肉无力和肌肉质量减少为特征，是在长期太空任务和卧床休息(例如病人)期间因失重而观察到的主要生理变化之一。萎缩和肌肉激活能力受损可能是停用引起的神经-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和兴奋-收缩耦合。神经营养因子和神经营养因子对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，导致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，也可能是由于脊柱上活动模式的改变所致。以上观察表明，神经肌肉相互作用是有效应对肌肉质量和功能丧失的关键靶点。在过去的几十年里，许多研究表明了各种对策的有效性，以防止微重力导致的肌肉萎缩。国际空间站(ISS)的宇航员目前每天花2.5小时进行宝贵的机组时间锻炼，以防止肌肉骨骼和心血管疾病。为了缩短日常锻炼时间和提高训练效率，需要为未来的长期任务探索替代对策。短臂离心机产生的人工重力是一种很有前途的新选择，它模拟了我们自然的1-G环境，并可能有效地保护肌肉骨骼系统。由于测试人体离心力的研究的第一批数据很有希望，欧洲航天局(ESA)目前与NASA合作进行了一系列卧床休息研究，以详细研究其对人体的影响及其作为对策的实施。我和包括曼彻斯特城市大学的汉斯·德根斯教授在内的五名国际同事一起，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个为期60天的卧床研究中。我们的实验包括1.肌肉组织和血液样本中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的相关性；4.人类离心机能在多大程度上阻止这些变化的分析。

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.