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Updated: Aug 18, 2026
Cryosectioning of Contiguous Regions of a Single Mouse Skeletal Muscle for Gene Expression and Histological Analyses
Published on: December 12, 2016
Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles
Tatiana Y Kostrominova1, Douglas E Dow, Robert G Dennis
1Institute of Gerontology, Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109-2007, USA. kostromi@umich.edu
Abstract:
Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A microarray study compared gene expression profiles of 2-mo denervated and control extensor digitorum longus (EDL) muscles from 6-mo-old rats. The study identified 121 genes with increased and 7 genes with decreased mRNA expression. The expression of 107 of these genes had not been identified previously as changed after denervation. Many of the genes identified were genes that are highly expressed in skeletal muscles during embryonic development, downregulated in adults, and upregulated after denervation of muscle fibers. Electrical stimulation of denervated muscles preserved muscle mass and maximal force at levels similar to those in the control muscles. To understand the processes underlying the effect of electrical stimulation on denervated skeletal muscles, mRNA and protein expression of a number of genes, identified by the microarray study, was compared. The hypothesis was that loss of nerve action potentials and muscle contractions after denervation play the major roles in upregulation of gene expression in skeletal muscles. With electrical stimulation of denervated muscles, the expression levels for these genes were significantly downregulated, consistent with the hypothesis that loss of action potentials and/or contractions contribute to the alterations in gene expression in denervated skeletal muscles.
Insights
Long-term muscle denervation causes significant gene expression changes, often reverting to embryonic patterns. Electrical stimulation helps restore muscle mass and force by downregulating these altered gene expressions.
Area of Science:
- Muscle physiology
- Molecular biology
- Neuroscience
Background:
- Skeletal muscle denervation leads to degeneration, atrophy, and force loss.
- These changes are accompanied by widespread alterations in gene mRNA expression.
- Understanding these molecular events is crucial for developing therapeutic strategies.
Purpose of the Study:
- To comprehensively identify molecular events in long-term denervated skeletal muscles.
- To investigate the role of nerve activity and muscle contractions in regulating gene expression post-denervation.
Main Methods:
- Microarray analysis of gene expression in denervated and control rat extensor digitorum longus (EDL) muscles.
- Comparison of mRNA and protein expression of selected genes after electrical stimulation of denervated muscles.
Main Results:
- 121 genes showed increased and 7 genes showed decreased mRNA expression in denervated muscles.
- 107 of these altered genes were previously unidentified in denervation studies.
- Many upregulated genes are typically expressed during embryonic development and downregulated in adult muscles.
- Electrical stimulation preserved muscle mass and force, and downregulated the expression of denervation-induced genes.
Conclusions:
- Muscle denervation triggers significant, previously unrecognized changes in gene expression, including the reactivation of embryonic gene programs.
- Loss of nerve action potentials and muscle contractions are key contributors to these gene expression alterations.
- Electrical stimulation can mitigate denervation-induced molecular changes, preserving muscle function, supporting the role of neural and mechanical activity.
