Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease
Autor(a) principal: | |
---|---|
Data de Publicação: | 2001 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/5802 https://doi.org/10.1006/nbdi.2001.0388 |
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. |
id |
RCAP_c7746718b6c75e6e738644c1bb691c41 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/5802 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's DiseaseHuntington's disease; lentiviral vector; gene therapy; ciliary neurotrophic factor; quinolinic acid lesion modelNeurodegenerative 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.http://www.sciencedirect.com/science/article/B6WNK-459HT27-6/1/34ed72189337f85bad52e94464dadd042001info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleaplication/PDFhttp://hdl.handle.net/10316/5802http://hdl.handle.net/10316/5802https://doi.org/10.1006/nbdi.2001.0388engNeurobiology of Disease. 8:3 (2001) 433-446Almeida, L. Pereira deZala, D.Aebischer, P.Déglon, N.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2021-11-11T10:43:28Zoai:estudogeral.uc.pt:10316/5802Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:23.734583Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
title |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
spellingShingle |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease Almeida, L. Pereira de Huntington's disease; lentiviral vector; gene therapy; ciliary neurotrophic factor; quinolinic acid lesion model |
title_short |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
title_full |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
title_fullStr |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
title_full_unstemmed |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
title_sort |
Neuroprotective Effect of a CNTF-Expressing Lentiviral Vector in the Quinolinic Acid Rat Model of Huntington's Disease |
author |
Almeida, L. Pereira de |
author_facet |
Almeida, L. Pereira de Zala, D. Aebischer, P. Déglon, N. |
author_role |
author |
author2 |
Zala, D. Aebischer, P. Déglon, N. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Almeida, L. Pereira de Zala, D. Aebischer, P. Déglon, N. |
dc.subject.por.fl_str_mv |
Huntington's disease; lentiviral vector; gene therapy; ciliary neurotrophic factor; quinolinic acid lesion model |
topic |
Huntington's disease; lentiviral vector; gene therapy; ciliary neurotrophic factor; quinolinic acid lesion model |
description |
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. |
publishDate |
2001 |
dc.date.none.fl_str_mv |
2001 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/5802 http://hdl.handle.net/10316/5802 https://doi.org/10.1006/nbdi.2001.0388 |
url |
http://hdl.handle.net/10316/5802 https://doi.org/10.1006/nbdi.2001.0388 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Neurobiology of Disease. 8:3 (2001) 433-446 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
aplication/PDF |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799133751148544000 |