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

• Applicant: Professorin Dr. Bergita Ganse
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Anatomy and Physiology ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409520867

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.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professor Dr. Hans Degens