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

Article type: Research Article

Authors: DeLucia, Tracey A.^; | Alexander, Thomas D. | Fargo, Keith N.^; | Jones, Kathryn J.^;

Affiliations: Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Maywood, IL 60153, USA | Research and Development Services, Hines VA Hospital, Hines, IL 60141, USA

Note: [] Corresponding author: Dr. Kathryn J. Jones, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Bldg 102, Rm 5653, Maywood, IL 60153, USA. Tel.: +1 708 202 5786; E-mail: [email protected], [email protected] and [email protected]

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.

Keywords: Red nucleus, spinal cord injury, olfactory ensheathing cell, Schwann cell, BDNF

Journal: Restorative Neurology and Neuroscience, vol. 25, no. 5-6, pp. 573-584, 2007