PMID- 18334774 OWN - NLM STAT- MEDLINE DCOM- 20080612 LR - 20131121 IS - 0922-6028 (Print) IS - 0922-6028 (Linking) VI - 25 IP - 5-6 DP - 2007 TI - Effects of single versus combinatorial treatment strategies on beta II-tubulin gene expression in axotomized hamster rubrospinal motoneurons. PG - 573-84 AB - PURPOSE: 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. FAU - DeLucia, Tracey A AU - DeLucia TA AD - Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Maywood, IL 60153, USA. linda.poggensee@va.gov FAU - Alexander, Thomas D AU - Alexander TD FAU - Fargo, Keith N AU - Fargo KN FAU - Jones, Kathryn J AU - Jones KJ LA - eng GR - NS44810/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. PL - Netherlands TA - Restor Neurol Neurosci JT - Restorative neurology and neuroscience JID - 9005499 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Tubulin) RN - WI93Z9138A (Testosterone Propionate) SB - IM MH - Animals MH - Axotomy/methods MH - Brain-Derived Neurotrophic Factor/therapeutic use MH - Cell Transplantation/methods MH - Cricetinae MH - Male MH - Mesocricetus MH - Motor Neurons/drug effects/*metabolism MH - Olfactory Mucosa/cytology MH - RNA, Messenger/metabolism MH - RNA, Small Interfering/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Schwann Cells/transplantation MH - Spinal Cord Injuries/*pathology/therapy MH - Testosterone Propionate/*pharmacology MH - Tubulin/*genetics/metabolism MH - Up-Regulation/drug effects/*physiology EDAT- 2008/03/13 09:00 MHDA- 2008/06/13 09:00 CRDT- 2008/03/13 09:00 PHST- 2008/03/13 09:00 [pubmed] PHST- 2008/06/13 09:00 [medline] PHST- 2008/03/13 09:00 [entrez] PST - ppublish SO - Restor Neurol Neurosci. 2007;25(5-6):573-84.