Long-term Training with Electrical Stimulation Regulates Muscle Gene Expression and Bone Architecture after Spinal Cord Injury

Abstract

Long-term training with electrical stimulation regulates muscle gene expression and bone architecture after SCI: Adams CM, Suneja M, McHenry CM, Littmann AL, Dudley-Javoroski S, Shields RK, Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa Background: Musculoskeletal deterioration is a serious secondary complication associated with paralysis from spinal cord injury (SCI). PURPOSE: We present the long-term effects of regular electrical stimulation training on muscle gene regulation and bone architecture after SCI. METHODS: Individuals with complete paralysis from SCI trained the calf muscle (soleus) or the thigh muscle (quadricep) during novel resistive tasks. The electrical stimulation protocol induced 2-4 bouts of 60-120 isometric contractions at a 15-20 Hz stimulation. After at least 2 years of unilateral training, we obtained muscle biopsies from the calf (soleus) and thigh muscles (vastus lateralis) of (trained and untrained) subjects with SCI. We then used Affymetrix human exon 1.0 arrays to identify mRNAs that were ≥ 1.5 fold increased or decreased in the atrophied untrained muscles. We next examined the trabecular bone using mDCT to quantify the sites and quality of the trabecular lattice. RESULTS: Out of >17,000 transcripts examined, in the untrained limb 51 mRNAs were increased including mRNAs encoding fast-twitch isoforms of myosin and troponin, as well as the mRNA encoding myostatin. Fifty-four mRNAs were decreased, including mRNAs encoding slow-twitch isoforms of myosin and troponin, 11 enzymes for oxidative phosphorylation, as well as PGC1α, a transcriptional co-activator that promotes the slow twitch, oxidative phenotype and inhibits FoxO3-mediated muscle atrophy. Training increased the mRNAs encoding slow-twitch isoforms and isoforms associated with glucose metabolism. The bone trabecular lattice was denser with distinct rods and plates within the trained femur and tibia. CONCLUSIONS: These findings support that thirty minutes/day of electrical stimulation stress induced significant muscle molecular adaptations and prevented the deterioration of bone after SCI. Funded by Nielsen Foundation and National Institutes of Health (R01-NR-01028505; R01-HD-04583233; R01HD062507).