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https://hdl.handle.net/10316/5802
Título: | Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease | Autor: | Almeida, L. Pereira de Zala, D. Aebischer, P. Déglon, N. |
Palavras-chave: | Huntington's disease; lentiviral vector; gene therapy; ciliary neurotrophic factor; quinolinic acid lesion model | Data: | 2001 | Citação: | Neurobiology of Disease. 8:3 (2001) 433-446 | Resumo: | Neurodegenerative diseases represent promising targets for gene therapy approaches provided effective transfer vectors. In the present study, we evaluated the effectiveness of LacZ-expressing lentiviral vectors with two different internal promoters, the mouse phosphoglycerate kinase 1 (PGK) and cytomegalovirus (CMV), to infect striatal cells. The intrastriatal injection of lenti-[beta]-Gal vectors lead to 207, 400 ± 11,500 and 303,100 ± 4,300 infected cells in adult rats, respectively. Importantly, the [beta]-galactosidase activity was higher in striatal extracts from PGK-LacZ-injected animals as compared to CMV-LacZ animals. The efficacy of the system was further examined with a potential therapeutic gene for the treatment of Huntington's disease, the human ciliary neurotrophic factor (CNTF). PGK-LacZ- or PGK-CNTF-expressing viruses were stereotaxically injected into the striatum of rats, 3 weeks later the animals were unilaterally lesioned with 180 nmol of quinolinic acid (QA). Control animals displayed 148 ± 43 apomorphine-induced rotations ipsilateral to the lesion 5 days postlesion as compared to 26 ± 22 turns/45 min in the CNTF-treated group. The extent of the striatal damage was significantly diminished in the CNTF-treated rats as indicated by the 52 ± 9.7% decrease of the lesion volume and the sparing of DARPP-32, ChAT and NADPH-d neuronal populations. These results further establish that lentiviruses may represent an efficient gene delivery system for the screening of therapeutic molecules in Huntington's disease. | URI: | https://hdl.handle.net/10316/5802 | DOI: | 10.1006/nbdi.2001.0388 | Direitos: | openAccess |
Aparece nas coleções: | FFUC- Artigos em Revistas Internacionais |
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