Medium-term Bed Rest Disrupts Motor Unit Properties and Neuromuscular Transmission in Young Adults

Background: Short-term disuse minimally affects higher-threshold motor units (MUs) and neuromuscular junction (NMJ) function, but the consequences of prolonged disuse on neuromuscular function remain unclear. This study examined how 21 days of bed rest impact MU properties, NMJ transmission, and NMJ morphology. We hypothesise that this disuse period impairs MU properties across different contraction intensities, and induces alterations in NMJ structure and function. Methods: Nine healthy young males (18–29 years) underwent 21 days of strict horizontal bed rest. Pre- (BR0) and post-bed rest (BR21), we assessed quadriceps maximal voluntary contraction (MVC) and muscle size. Intramuscular (iEMG) and high-density surface electromyography (HDsEMG) were used to evaluate MU properties at 25% and 50% MVC. NMJ transmission was assessed electrophysiologically via near-fibre jiggle and segment jitter, while NMJ morphology was analyzed from muscle biopsies. Serum C-terminal agrin fragment (CAF), a biomarker of NMJ remodeling, was also measured. Results: Quadriceps MVC and size significantly decreased at BR21. MU discharge rate declined, MU potential area changed, and complexity increased at both contraction intensities, overall indicating alterations in MU properties. NMJ transmission impairment was detected at 25% MVC, with increased near-fibre jiggle and segment jitter. Serum CAF levels were elevated at BR21, corroborating NMJ remodeling. Notably, NMJ morphological analysis revealed denervated NMJs exclusively at BR21. Conclusion: Medium-term disuse alters MU properties, impairs NMJ transmission, and triggers early NMJ remodeling, including signs of denervation. These findings highlight disuse duration as a key factor and reinforce the need for countermeasures in clinical, rehabilitation, and spaceflight contexts. Space It Up project funded by the Italian Space Agency, ASI, and the Ministry of University and Research, MUR, under contract n. 2024-5-E.0 - CUP n. I53D24000060005 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.