title: A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury.
abstract: Paralysis after a spinal cord injury (SCI) induces physiological adaptations that compromise the musculoskeletal and metabolic systems. Unlike non-SCI individuals, people with spinal cord injury experience minimal muscle activity which compromises optimal glucose utilization and metabolic control. Acute or chronic muscle activity, induced through electrical stimulation, may regulate key genes that enhance oxidative metabolism in paralyzed muscle. We investigated the short and long term effects of electrically induced exercise on mRNA expression of human paralyzed muscle. We developed an exercise dose that activated the muscle for only 0.6% of the day. The short term effects were assessed 3 hours after a single dose of exercise, while the long term effects were assessed after training 5 days per week for at least one year (adherence 81%). We found a single dose of exercise regulated 117 biological pathways as compared to 35 pathways after one year of training. A single dose of electrical stimulation increased the mRNA expression of transcriptional, translational, and enzyme regulators of metabolism important to shift muscle toward an oxidative phenotype (PGC-1α, NR4A3, IFRD1, ABRA, PDK4). However, chronic training increased the mRNA expression of specific metabolic pathway genes (BRP44, BRP44L, SDHB, ACADVL), mitochondrial fission and fusion genes (MFF, MFN1, MFN2), and slow muscle fiber genes (MYH6, MYH7, MYL3, MYL2). These findings support that a dose of electrical stimulation (∼10 minutes/day) regulates metabolic gene signaling pathways in human paralyzed muscle. Regulating these pathways early after SCI may contribute to reducing diabetes in people with longstanding paralysis from SCI.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Petrie
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Manish
authors.initials: M
authors.lastname: Suneja
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Faidley
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America; Department of Veterans Affairs, VA Medical Center, Iowa City, Iowa, United States of America.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Shields
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D004599:Electric Stimulation Therapy; D015444:Exercise / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009142:Musculoskeletal Physiological Phenomena; D020411:Oligonucleotide Array Sequence Analysis; D010243:Paralysis / Q000150:complications* / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000209:etiology* / Q000473:pathology / Q000534:rehabilitation*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger