Effects of single versus combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons

Tracey A. DeLucia, Thomas D. Alexander, Keith N. Fargo, Kathryn Jones

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: βII-tubulin, a regeneration-associated gene, is upregulated in injured peripheral neurons, but significantly less so in injured central neurons. Using a hamster dorsal spinal cord injury (SCI), the ability of single versus combinatorial treatment strategies to alter βII-tubulin mRNA expression in rubrospinal motoneurons (RSMN) was examined. We have shown that systemic testosterone propionate (TP) treatment in combination with peripheral nerve grafting into a SCI site produces a peripheral-like pattern of βII-tubulin mRNA expression in injured RSMN. In the present study, selected single- and combinatorial-therapy strategies were tested for their ability to promote a sustained upregulation of βII-tubulin mRNA levels in injured RSMN. Methods: Single treatments of olfactory ensheathing cells (OEC), brain-derived neurotrophic factor (BDNF), or Schwann cells (SC) vs combinatorial treatments (SC + TP, OEC + TP, and OEC + BDNF) were administered to hamsters following a dorsal SCI. Quantitative in situ hybridization in conjunction with a βII-tubulin cDNA probe was accomplished. Results: All of the single-therapy treatments tested were able to prevent the downregulation of βII-tubulin mRNA that occurred a week after injury alone, but only BDNF maintained high levels of βII-tubulin mRNA. In contrast, all combinatorial treatments tested maintained the upregulation of βII-tubulin mRNA expression in injured RSMN 1 week post-SCI. Conclusions: Targeting both intrinsic and extrinsic components of CNS injury can re-program elements of the molecular response of injured central motoneurons.

Original languageEnglish (US)
Pages (from-to)573-584
Number of pages12
JournalRestorative Neurology and Neuroscience
Volume25
Issue number5-6
StatePublished - 2007
Externally publishedYes

Fingerprint

Motor Neurons
Tubulin
Cricetinae
Gene Expression
Spinal Cord Injuries
Testosterone Propionate
Messenger RNA
Brain-Derived Neurotrophic Factor
Schwann Cells
Up-Regulation
Neurons
Wounds and Injuries
Response Elements
Peripheral Nerves
In Situ Hybridization
Regeneration
Down-Regulation
Complementary DNA
Therapeutics
Genes

Keywords

  • BDNF
  • Olfactory ensheathing cell
  • Red nucleus
  • Schwann cell
  • Spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

Cite this

Effects of single versus combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons. / DeLucia, Tracey A.; Alexander, Thomas D.; Fargo, Keith N.; Jones, Kathryn.

In: Restorative Neurology and Neuroscience, Vol. 25, No. 5-6, 2007, p. 573-584.

Research output: Contribution to journalArticle

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