Neuromuscular junction instability with inactivity

The neuromuscular junction (NMJ) plays a key role in modulating muscle contraction,but the impact of short-term disuse on NMJ structure and function, particularly in older humans,remains unclear. This study aimed to investigate NMJ alterations following 10 days of horizontalbed rest in 10 older males (68.5 ± 2.6 years). Before and after bed rest, vastus lateralis musclebiopsies were obtained to evaluate NMJ morphology, intramuscular EMG (iEMG) was recordedto assess NMJ function and blood samples were collected to determine circulating C-terminal agrinfragment (CAF) concentration, a biomarker of NMJ remodelling. In a sub-cohort of six participantswho had NMJs in both pre- and post-bed rest biopsies, we observed altered NMJ morphology,including reduced overlap between NMJ terminals, as well as increased endplate area and peri-meter. CAF concentration was elevated after bed rest, suggesting ongoing NMJ remodelling. iEMGanalysis showed increased motor unit potential complexity and reduced firing rate. In addition,we observed impaired NMJ transmission, inferred from increased near-fibre jiggle and segmentjitter. These findings suggest that older male individuals are susceptible to NMJ remodelling andimpaired transmission with short-term disuse, providing valuable insights into the morphologicaland functional consequences of inactivity in an ageing population. Our study highlights theimportance of developing interventions for mitigating the detrimental consequences of inactivityon neuromuscular health in older adults, which they frequently experience following injury, trauma,illness or surgery.