Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axons
| Autor: | Bernard L. Schneider, Rafael J. Yáñez-Muñoz, Sherif G. Ahmed, Anna Y Allan, John H. Rogers, Elizabeth M. Muir, Rong-Rong Zhao, Joost Verhaagen, Jean-Charles Bensadoun, João Nuno Alves, James W. Fawcett, Kasper C. D. Roet, Hannah Rickman, Roger J. Keynes, Jessica C. F. Kwok |
|---|---|
| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN) |
| Rok vydání: | 2011 |
| Předmět: |
System
Male Chondroitinase ABC Pyramidal Tracts CSPG chondroitin sulfate proteoglycan Chondroitin ABC Lyase GAG glycosaminoglycan LV-ChABC lentiviral vector encoding chondroitinase ABC Mice 0302 clinical medicine Functional Recovery Axon CST corticospinal tract Spinal cord injury Gene-Transfer Cells Cultured Cerebral Cortex 0303 health sciences DMEM Dulbecco's modified Eagle's medium General Neuroscience Brain 3. Good health medicine.anatomical_structure medicine.symptom Delivery Plasticity Cells Neuroscience(all) Genetic Vectors Central nervous system Chondroitin ABC lyase Transgene Expression Biology CNS central nervous system Gene Expression Regulation Enzymologic Article Viral vector CS chondroitin sulfate Lesion 03 medical and health sciences PBS phosphate buffered saline PGK phosphoglycerate kinase medicine Animals Humans Axon regeneration Spinal Cord Injuries 030304 developmental biology Sheep Pyramidal tracts Spinal-Cord-Injury Lentivirus CMV cytomegalovirus Lentiviral vectors BDA biotinylated dextran amine medicine.disease Corticospinal tract Nerve Regeneration Rats HEK293 Cells nervous system Therapy Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Methods, 201, 228-238. Elsevier B.V. Journal of Neuroscience Methods Journal of Neuroscience Methods; Vol 201 |
| ISSN: | 0165-0270 |
| DOI: | 10.1016/j.jneumeth.2011.08.003 |
| Popis: | Highlights ► Lentiviral vectors can transduce neurons and glia to secrete chondroitinase. ► The active enzyme is secreted from long-distance axon projections from the cerebral cortex. ► Chondroitinase transduction promotes preservation and sprouting of damaged corticospinal axons. Several diseases and injuries of the central nervous system could potentially be treated by delivery of an enzyme, which might most effectively be achieved by gene therapy. In particular, the bacterial enzyme chondroitinase ABC is beneficial in animal models of spinal cord injury. We have adapted the chondroitinase gene so that it can direct secretion of active chondroitinase from mammalian cells, and inserted it into lentiviral vectors. When injected into adult rat brain, these vectors lead to extensive secretion of chondroitinase, both locally and from long-distance axon projections, with activity persisting for more than 4 weeks. In animals which received a simultaneous lesion of the corticospinal tract, the vector reduced axonal die-back and promoted sprouting and short-range regeneration of corticospinal axons. The same beneficial effects on damaged corticospinal axons were observed in animals which received the chondroitinase lentiviral vector directly into the vicinity of a spinal cord lesion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect