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Electrical Stimulation Accelerates and Enhances Expression of Regeneration-Associated Genes in Regenerating Rat Femoral Motoneurons
Open accessAbstract
1. In this study we investigated whether electrical stimulation accelerates the upregulation of Talpha1-tubulin and GAP-43 (regeneration-associated genes; RAGs) and the downregulation of the medium-molecular-weight neurofilament (NFM), in concert with stimulation-induced acceleration of BDNF and trkB gene expression and axonal regeneration. 2. Two weeks prior to unilateral femoral nerve transection and suture, fluorogold (Fluorochrome Inc., Denver) or fluororuby (Dextran tetramethylrhodamine, Mol. Probes, D-1817, Eugene, OR) was injected into quadriceps muscles of the left and right hindlimbs to label the femoral motoneuron pools as previously described. Over a period of 7 days, fresh spinal cords were processed for semiquantitation of mRNA by using in situ hybridization. 3. There was an increase in Talpha1-tubulin and GAP-43 mRNA and a decline in the NFM mRNA at 7 days after nerve suture and sham stimulation but not in intact nerves. In contrast, 1-h stimulation of sutured but not intact nerves dramatically accelerated the changes in gene expression: mRNA levels of Talpha1-tubulin and GAP-43 were significantly elevated above control levels by 2 days while NFM mRNA was significantly reduced by 2 days in the sutured nerves. Thereby, the neurofilament/tubulin expression ratio was reduced at 2 days after suture and stimulation, possibly allowing more tubulin to be transported faster into the growing axons to accelerate the elongation rate following stimulation. Importantly, the changes in RAGs and NFM gene expression were delayed relative to the accelerated upregulation of BDNF and trkB mRNA by electrical stimulation. 4. The temporal sequence of upregulation of BDNF and trkB, altered gene expression of RAGs and NFM, and accelerated axonal outgrowth from the proximal nerve stump are consistent with a key role of BDNF and trkB in mediating the altered expression of RAGs and, in turn, the promotion of axonal outgrowth after electrical stimulation.
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Self-citation
Metadata
- Authors
- Al-Majed, A. A., Tam, S. L., & Gordon, T.
- Affiliations
- University of Alberta (CA)
- Corresponding author
- Gordon, Tessa
- ORCID
- Gordon, Tessa
- Venue
- Cellular and Molecular Neurobiology
- Published
- 2004-06
- Volume
- 24
- Issue
- 3
- Pages
- 379-402
- ISSN
- 0272-4340 (ISSN-L)
- 1573-6830
- PMC
- PMC11529956
- OpenAlex
- W2098572051
- Cited by
- 292
- References
- 38
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 18 · 2023: 17 · 2022: 15 · 2021: 10 · 2020: 19 · 2019: 17 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 15 · 2014: 11 · 2013: 11 · 2012: 15
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Neurobiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- King Saud University
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Keywords
- electrical stimulation, axon regeneration, regeneration-associated genes, GAP-43, neurofilaments, brain-derived neurotrophic factor, TrkB, nerve transection, axon growth, gene expression, spinal cord
- MeSH terms
- Animals, Disease Models, Animal, Electric Stimulation Therapy, Female, Femoral Nerve, Gene Expression Regulation, Motor Neurons, Nerve Regeneration, Nerve Tissue Proteins, RNA, Messenger, Tubulin, Down-Regulation, Up-Regulation, Neurofilament Proteins, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Axotomy, GAP-43 Protein, Growth Cones, Receptor, trkB, Rats
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