HSV-mediated Transfer of Artemin Overcomes Myelin Inhibition to Improve Outcome After Spinal Cord Injury
| Autor: | Zhigang Zhou, Marina Mata, Xiangmin Peng, David J. Fink |
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| Rok vydání: | 2009 |
| Předmět: |
Neurite
Blotting Western Genetic Vectors Carbazoles Artemin Nerve Tissue Proteins Cell Line Rats Sprague-Dawley Dorsal root ganglion Neurotrophic factors Ganglia Spinal Drug Discovery Neurites Genetics Glial cell line-derived neurotrophic factor medicine Animals Simplexvirus Pyrroles Enzyme Inhibitors Phosphorylation Cyclic AMP Response Element-Binding Protein Molecular Biology Spinal cord injury Cells Cultured Spinal Cord Injuries Neurons Pharmacology Arginase biology Reverse Transcriptase Polymerase Chain Reaction Immunochemistry Original Articles Genetic Therapy medicine.disease Spinal cord Cyclic AMP-Dependent Protein Kinases Axons Rats Cell biology medicine.anatomical_structure Spinal Cord Biochemistry biology.protein Molecular Medicine Female GDNF family of ligands Myelin Proteins |
| Zdroj: | Molecular Therapy. 17:1173-1179 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/mt.2009.52 |
| Popis: | Artemin is a neurotrophic factor of the glial cell line-derived neurotrophic factor (GDNF) family of ligands that acts through the GDNF family receptor alpha3 (GFRalpha3)/ret receptor found predominantly on sensory and sympathetic neurons. In order to explore the potential utility of artemin to improve functional outcome after spinal cord injury (SCI), we constructed a nonreplicating herpes simplex virus (HSV)-based vector to express artemin (QHArt). We found that QHArt efficiently transfects spinal cord neurons to produce artemin. Transgene-mediated artemin supported the extension of neurites by primary dorsal root ganglion neurons in culture, and allowed those cells to overcome myelin inhibition of neurite extension through activation of protein kinase A (PKA) to phosphorylate cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and increase expression of arginase I. Intraspinal injection of QHArt immediately after thoracic spinal cord dorsal over hemisection produced a statistically significant improvement in motor recovery over the course of four weeks measured by locomotor rating score. |
| Databáze: | OpenAIRE |
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