A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury

Michael A Petrie; Manish Suneja; Elizabeth Faidley; Richard K Shields

doi:10.1371/journal.pone.0115791

Back

A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury

Journal article

Open access

Peer reviewed

A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury

Michael A Petrie, Manish Suneja, Elizabeth Faidley and Richard K Shields

PloS one, Vol.9(12), pp.e115791-e115791

2014

DOI: 10.1371/journal.pone.0115791

PMCID: PMC4274164

PMID: 25531450

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0115791View

Published (Version of record) Open Access

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.

Signal Transduction

Biomarkers - metabolism

Oligonucleotide Array Sequence Analysis

Humans

RNA, Messenger - genetics

Spinal Cord Injuries - etiology

Gene Expression Regulation

Adaptation, Physiological - physiology

Muscle, Skeletal - metabolism

Gene Expression Profiling

Paralysis - genetics

Musculoskeletal Physiological Phenomena

Electric Stimulation Therapy

Gene Regulatory Networks

Reverse Transcriptase Polymerase Chain Reaction

Paralysis - complications

Spinal Cord Injuries - pathology

Adult

Spinal Cord Injuries - rehabilitation

Exercise - physiology

Muscle, Skeletal - pathology

Real-Time Polymerase Chain Reaction

Details

Title: Subtitle: A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury
Creators: Michael A Petrie - Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America
Manish Suneja - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America
Elizabeth Faidley - Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America
Richard K Shields - 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
Resource Type: Journal article
Publication Details: PloS one, Vol.9(12), pp.e115791-e115791
DOI: 10.1371/journal.pone.0115791
PMID: 25531450
PMCID: PMC4274164
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01HD062507 / NICHD NIH HHS I01 RX000149 / RRD VA R01 HD062507 / NICHD NIH HHS
Language: English
Date published: 2014
Academic Unit: Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science; Nephrology; Internal Medicine
Record Identifier: 9984047637502771

Metrics

27 Record Views

26 Times Cited - Web of Science

See more details