Early Biomarkers of Muscle Atrophy and of Neuromuscular Alterations During 10‐Day Bed Rest

Introduction Disuse atrophy may not only arise from a reduction in mechanical loading but also from muscle denervation and neuromuscular junction damage, triggered by inactivity , . The identification of biomarkers of muscle atrophy and of neuromuscular degeneration is therefore needed for an early detection of neuromuscular alterations induced by inactivity. The aim of this study was to investigate the onset of muscle atrophy and of neuromuscular alterations during a short‐term inactivity period. Methods Ten healthy males (aged 23±5 years) participated to a 10‐day bed rest (BR) study, after Ethical approval and informed consent. Blood samples were collected every two days for the assessment of NMJ damage from serum levels of c‐terminal agrin fragment (CAF). Muscle fibre denervation was determined from the expression of neural cell adhesive molecule (N‐CAM) in myofibres obtained from vastus lateralis (VL) muscle biopsies at baseline, 5 and 10 days of BR. Myofibre atrophy was assessed from mean fibre cross‐sectional area (CSA). Whole muscle atrophy was assessed from measurements of muscle architecture (pennation angle and muscle CSA) every two days of BR using ultrasonography. Significance of differences was tested with repeated‐measures Anova, level of significance was set at p<0.05. Results Atrophy of whole muscle and of myofibers, represented by decreases of 5.8% in muscle CSA (P<0.0001), 7.3% in pennation angle (P<0.0001), and by a 21% reduction in mean fibre CSA (P<0.01) were detected after 10 days of BR. A 19% increase (p<0.01) in CAF levels was found on BR day 10, together with a 18‐fold increase in N‐CAM positive myofibres. The analysis of myofiber CSA and N‐CAM expression at BR 5 day is in progress. Conclusions These findings show a very early onset (within 10 days) of whole muscle and fiber atrophy accompanied by NMJ damage and myofiber denervation in response to chronic inactivity. We suggest that countermeasures against neuromuscular maladaptation to chronic inactivity ought to be implemented as early as possible. Support or Funding Information Funding by ASI, MARS‐PRE Project, n. DC‐VUM‐2017‐006 , is acknowledged.