Impact of bed rest-induced inactivity on cellular stress and neuromuscular junctions in young adults

Prolonged bed rest induces significant neuromuscular and metabolic adaptations that may differ between sexes, potentially influencing recovery and rehabilitation outcomes. Understanding sex-specific responses is essential for developing targeted countermeasures against muscle deconditioning and neuromuscular impairment associated with physical inactivity. The aim of this study was to investigate cellular stress and electrophysiological alterations of the motor unit (MU) and neuromuscular junction (NMJ) following bed rest, with particular focus on potential differences between males and females. Eleven healthy young males and nine healthy young females underwent 21 days of bed rest. Quadriceps Femoris (QF) strength and MU activity were measured during voluntary isometric contractions, while circulating biomarkers of NMJ instability (c-terminal agrin fragment, CAF) and cellular stress (Fibroblast Growth Factor 21, FGF21) were evaluated through immunoassays. QF muscle strength (maximum voluntary contraction, MVC) and firing rate decreased significantly in both groups after bed rest. Motor unit potential (MUP) area was significantly reduced only in males, together with increased near-fibre motor unit (NFM) jiggle, suggesting impaired NMJ function. CAF increased in both groups, indicating molecular instability of the NMJ. Baseline FGF21 concentrations were higher in females than males, and both groups showed significant reductions over time, with a greater decrease in females. These findings demonstrate both shared and sex-specific possible adaptations to bed rest. Females exhibited stronger metabolic responses, whereas males showed greater electrophysiological disruption, suggesting higher NMJ vulnerability. These results also highlight the importance of sex-specific rehabilitation strategies to optimize recovery and preserve neuromuscular health following prolonged inactivity.