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:
kathy.jones2@va.gov, knfargo@gmail.com and linda.poggensee@va.gov
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.
