Deleterious impacts of inactivity and beneficial impacts of neuromuscular electrical stimulation on muscle structure and function in the zebrafish model of Duchenne Muscular Dystrophy

Although it is known that inactivity is deleterious for healthy individuals, less is known about the consequences of inactivity on muscle disease. Reduced activity is frequently encouraged for individuals with congenital muscular dystrophies such as Duchenne Muscular Dystrophy (DMD). We used the zebrafishdmdmutant and a longitudinal design to elucidate the consequences of inactivity versus activity on muscle health. Inactivity worsened muscle structure and survival. We designed four neuromuscular stimulation paradigms loosely based on weight lifting regimens. Each paradigm differentially affected muscle structure, function, and survival. Only endurance neuromuscular stimulation (eNMES) improved all outcome measures. We found that eNMES (1) returns gene expression to wild-type levels, (2) increases muscle adhesion to the extracellular matrix (ECM), and (3) remodels the ECM and supports regeneration. Our data indicate that inactivity is deleterious but neuromuscular stimulation can be beneficial, suggesting that the right type of activity may benefit patients with muscle disease.