Genomic and Epigenomic Evaluation of Electrically Induced Exercise in People With Spinal Cord Injury: Application to Precision Rehabilitation

Abstract

Abstract Objective Physical therapists develop patient-centered exercise prescriptions to help overcome the physical, emotional, psychosocial, and environmental stressors that undermine a person’s health. Optimally prescribing muscle activity for people with disability, such as a spinal cord injury, is challenging because of their loss of volitional movement control and the deterioration of their underlying skeletal systems. This report summarizes spinal cord injury–specific factors that should be considered in patient-centered, precision prescription of muscle activity for people with spinal cord injury. This report also presents a muscle genomic and epigenomic analysis to examine the regulation of the proliferator-activated receptor γ coactivator 1α (PGC-1α) (oxidative) and myostatin (hypertrophy) signaling pathways in skeletal muscle during low-frequency (lower-force) electrically induced exercise versus higher-frequency (higher-force) electrically induced exercise under constant muscle recruitment (intensity). Methods Seventeen people with spinal cord injury participated in 1 or more unilateral electrically induced exercise sessions using a lower-force (1-, 3-, or 5-Hz) or higher-force (20-Hz) protocol. Three hours after the exercise session, percutaneous muscle biopsies were performed on exercised and nonexercised muscles for genomic and epigenomic analysis. Results We found that low-frequency (low-force) electrically induced exercise significantly increased the expression of PGC-1α and decreased the expression of myostatin, consistent with the expression changes observed with high-frequency (higher-force) electrically induced exercise. Further, we found that low-frequency (lower-force) electrically induced exercise significantly demethylated, or epigenetically promoted, the PGC-1α signaling pathway. A global epigenetic analysis showed that >70 pathways were regulated with low-frequency (lower-force) electrically induced exercise. Conclusion These novel results support the notion that low-frequency (low-force) electrically induced exercise may offer a more precise rehabilitation strategy for people with chronic paralysis and severe osteoporosis. Future clinical trials are warranted to explore whether low-frequency (lower-force) electrically induced exercise training affects the overall health of people with chronic spinal cord injury.