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Cited by 292Nerve injury and regenerationNeuroscience and Neural EngineeringSpinal Cord Injury Research

Electrical Stimulation Accelerates and Enhances Expression of Regeneration-Associated Genes in Regenerating Rat Femoral Motoneurons

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Al-Majed, Abdulhakeem A., Tam, Siu Lin, Gordon, Tessa·2004·Cellular and Molecular Neurobiology
DOI 10.1023/b:cemn.0000022770.66463.f7PMC PMC11529956
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Abstract

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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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
Publisher
Springer Science and Business Media LLC
Published
2004-06
Volume
24
Issue
3
Pages
379-402
ISSN
  • 0272-4340 (ISSN-L)
  • 1573-6830
DOI
10.1023/b:cemn.0000022770.66463.f7
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
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 › Pathology and Forensic Medicine › 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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