Neuroprotective effect of a CNTF-expressing lentiviral vector in the quinolinic acid rat model of Huntington's disease

Autor: Nicole Déglon, Diana Zala, Patrick Aebischer, L. Pereira de Almeida
Rok vydání: 2001
Předmět:
Genetic enhancement
Wistar
Cytomegalovirus
Gene Expression
Ciliary neurotrophic factor
Pharmacology
chemistry.chemical_compound
Phosphoglycerate Kinase/genetics
Phosphoglycerate kinase 1
Promoter Regions
Genetic
education.field_of_study
biology
Huntington's disease
gene therapy
Huntington Disease
Neuroprotective Agents
Neurology
Gene Therapy/ methods
Female
Promoter Regions (Genetics)
medicine.symptom
Ciliary Neurotrophic Factor/ genetics
Genetic Vectors
Lentivirus/ genetics
lentiviral vector
ciliary neurotrophic factor
quinolinic acid lesion model
Gene delivery
Viral vector
lcsh:RC321-571
Lesion
medicine
Animals
Ciliary Neurotrophic Factor
beta-Galactosidase/genetics
Rats
Wistar
education
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Huntington Disease/chemically induced/ therapy
Animal
Lentivirus
Genetic Therapy
Quinolinic Acid
medicine.disease
beta-Galactosidase
Molecular biology
Cytomegalovirus/genetics
Rats
Disease Models
Animal
Phosphoglycerate Kinase
chemistry
Disease Models
biology.protein
Quinolinic acid
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Neurobiology of Disease, Vol 8, Iss 3, Pp 433-446 (2001)
ISSN: 0969-9961
Popis: 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. http://www.sciencedirect.com/science/article/B6WNK-459HT27-6/1/34ed72189337f85bad52e94464dadd04
Databáze: OpenAIRE
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