Abstract
In humans, spinal cord injury (SCI) induces deleterious changes in skeletal muscle that may be prevented or reversed by electrical stimulation muscle training. The molecular mechanisms underlying muscle stimulation training remain unknown. We studied two unique SCI subjects whose right soleus received >6 years of training (30 minutes/day, 5 days/week). Training preserved torque, fatigue index, contractile speed, and cross-sectional area in the trained leg, but not the untrained leg. Training decreased 10 mRNAs required for fast-twitch contractions and mRNA that encodes for myostatin, an autocrine/paracrine hormone that inhibits muscle growth. Conversely, training increased 69 mRNAs that mediate the slow-twitch, oxidative phenotype, including PGC-1α, a transcriptional coactivator that inhibits muscle atrophy. When we discontinued right soleus training, training-induced effects diminished slowly, with some persisting for >6 months. Training of paralyzed muscle induces localized and long-lasting changes in skeletal muscle mRNA expression that improve muscle mass and function.