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Updated: Apr 3, 2026
Activity-based Training on a Treadmill with Spinal Cord Injured Wistar Rats
Published on: January 16, 2019
Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor
Celine Baligand1, Yi-Wen Chen2, Fan Ye3
1Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
Abstract:
The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and corrected with treadmill training. The BMP pathway was differentially activated with early treadmill training as shown by Ingenuity Pathway Analysis. The expression of several muscle mass regulators was modulated by treadmill training, including Fst, Jun, Bmpr2, Actr2b, and Smad3. In addition, key players in fatty acids metabolism (Lpl and Fabp3) responded to both SCI induced inactivity and reloading with training. The decrease in Smad3 and Fst early after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFβ/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training.
Insights
Treadmill training after spinal cord injury (SCI) helps correct muscle remodeling by altering protein ubiquitination and mitochondrial function pathways. This approach also activates the BMP pathway and modulates key muscle mass regulators.
Area of Science:
- Molecular Biology
- Neuroscience
- Exercise Physiology
Background:
- Spinal cord injury (SCI) leads to significant muscle mass and function changes.
- The underlying genetic and molecular mechanisms of muscle remodeling post-SCI and during therapeutic interventions remain incompletely understood.
- Identifying these pathways is crucial for developing effective rehabilitation strategies.
Purpose of the Study:
- To identify key molecular pathways involved in muscle remodeling following SCI.
- To investigate the molecular effects of locomotor training (treadmill training) on SCI-induced muscle changes.
- To understand the role of specific signaling pathways and gene expression in muscle recovery.
Main Methods:
- Utilized a well-characterized rat model of moderate SCI.
- Implemented treadmill training as a locomotor therapeutic approach.
- Performed genome-wide expression profiling on soleus muscles at 3, 8, and 14 days post-SCI.
- Analyzed data using Ingenuity Pathway Analysis (IPA) and confirmed key findings with RT-PCR.
Main Results:
- SCI altered protein ubiquitination and mitochondrial function pathways, which were corrected by treadmill training.
- The Bone Morphogenetic Protein (BMP) pathway was differentially activated by early treadmill training.
- Treadmill training modulated the expression of muscle mass regulators (Fst, Jun, Bmpr2, Actr2b, Smad3) and fatty acid metabolism genes (Lpl, Fabp3).
Conclusions:
- Treadmill training effectively counteracts SCI-induced alterations in muscle molecular pathways.
- TGFβ/Smad3 signaling appears involved in SCI-induced muscle mass reduction.
- BMP pathway activation is associated with treadmill training, suggesting a role in muscle recovery and adaptation.
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