Effects of single versus combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons.
OBJECTIVE
betaII-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 betaII-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 betaII-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 betaII-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 betaII-tubulin cDNA probe was accomplished.


RESULTS
All of the single-therapy treatments tested were able to prevent the downregulation of betaII-tubulin mRNA that occurred a week after injury alone, but only BDNF maintained high levels of betaII-tubulin mRNA. In contrast, all combinatorial treatments tested maintained the upregulation of betaII-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.
DeLucia
Tracey A
TA
Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Maywood, IL 60153, USA. linda.poggensee@va.gov
Alexander
Thomas D
TD
Fargo
Keith N
KN
Jones
Kathryn J
KJ
D000818:Animals; D019771:Axotomy / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use; D017690:Cell Transplantation / Q000379:methods; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000637:transplantation; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000628:therapy; D043343:Testosterone Propionate / Q000494:pharmacology*; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014404:Tubulin; D043343:Testosterone Propionate