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Genomic and Epigenomic Evaluation of Electrically Induced Exercise in People With Spinal Cord Injury: Application to Precision Rehabilitation
Journal article   Open access   Peer reviewed

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

Michael A. Petrie, Eric B. Taylor, Manish Suneja and Richard K. Shields
Physical therapy, Vol.102(1), pzab243
01/01/2022
DOI: 10.1093/ptj/pzab243
PMCID: PMC8754383
PMID: 34718779
url
https://doi.org/10.1093/ptj/pzab243View
Published (Version of record) Open Access

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 gamma coactivator 1 alpha (PGC-1 alpha) (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-1 alpha 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-1 alpha 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.
Orthopedics Life Sciences & Biomedicine Rehabilitation Science & Technology

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