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Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF.
Exp Neurol. 2000 Jul; 164(1):15-24.EN

Abstract

Local delivery of therapeutic molecules represents one of the limiting factors for the treatment of neurodegenerative disorders. In vivo gene transfer using viral vectors constitutes a powerful strategy to overcome this limitation. The aim of the present study was to validate the lentiviral vector as a gene delivery system in the mouse midbrain in the perspective of screening biotherapeutic molecules in mouse models of Parkinson's disease. A preliminary study with a LacZ-encoding vector injected above the substantia nigra of C57BL/6j mice indicated that lentiviral vectors can infect approximately 40,000 cells and diffuse over long distances. Based on these results, glial cell line-derived neurotrophic factor (GDNF) was assessed as a neuroprotective molecule in a 6-hydroxydopamine model of Parkinson's disease. Lentiviral vectors carrying the cDNA for GDNF or mutated GDNF were unilaterally injected above the substantia nigra of C57BL/6j mice. Two weeks later, the animals were lesioned ipsilaterally with 6-hydroxydopamine into the striatum. Apomorphine-induced rotation was significantly decreased in the GDNF-injected group compared to control animals. Moreover, GDNF efficiently protected 69.5% of the tyrosine hydroxylase-positive cells in the substantia nigra against 6-hydroxydopamine-induced toxicity compared to 33.1% with control mutated GDNF. These data indicate that lentiviral vectors constitute a powerful gene delivery system for the screening of therapeutic molecules in mouse models of Parkinson's disease.

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Authors+Show Affiliations

Bensadoun JC
Division of Surgical Research and Gene Therapy Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Déglon N
No affiliation info available
Tseng JL
No affiliation info available
Ridet JL
No affiliation info available
Zurn AD
No affiliation info available
Aebischer P
No affiliation info available

MeSH

AnimalsApomorphineCell CountCorpus StriatumDopamineGenes, ReporterGenetic TherapyGenetic VectorsGlial Cell Line-Derived Neurotrophic FactorLentivirusMaleMesencephalonMiceMice, Inbred C57BLMicroinjectionsMotor ActivityNerve Growth FactorsNerve Tissue ProteinsOxidopamineParkinson Disease, SecondarySubstantia NigraTyrosine 3-Monooxygenase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10877911

Citation

Bensadoun, J C., et al. "Lentiviral Vectors as a Gene Delivery System in the Mouse Midbrain: Cellular and Behavioral Improvements in a 6-OHDA Model of Parkinson's Disease Using GDNF." Experimental Neurology, vol. 164, no. 1, 2000, pp. 15-24.
Bensadoun JC, Déglon N, Tseng JL, et al. Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF. Exp Neurol. 2000;164(1):15-24.
Bensadoun, J. C., Déglon, N., Tseng, J. L., Ridet, J. L., Zurn, A. D., & Aebischer, P. (2000). Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF. Experimental Neurology, 164(1), 15-24.
Bensadoun JC, et al. Lentiviral Vectors as a Gene Delivery System in the Mouse Midbrain: Cellular and Behavioral Improvements in a 6-OHDA Model of Parkinson's Disease Using GDNF. Exp Neurol. 2000;164(1):15-24. PubMed PMID: 10877911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lentiviral vectors as a gene delivery system in the mouse midbrain: cellular and behavioral improvements in a 6-OHDA model of Parkinson's disease using GDNF. AU - Bensadoun,J C, AU - Déglon,N, AU - Tseng,J L, AU - Ridet,J L, AU - Zurn,A D, AU - Aebischer,P, PY - 2000/7/6/pubmed PY - 2000/8/19/medline PY - 2000/7/6/entrez SP - 15 EP - 24 JF - Experimental neurology JO - Exp Neurol VL - 164 IS - 1 N2 - Local delivery of therapeutic molecules represents one of the limiting factors for the treatment of neurodegenerative disorders. In vivo gene transfer using viral vectors constitutes a powerful strategy to overcome this limitation. The aim of the present study was to validate the lentiviral vector as a gene delivery system in the mouse midbrain in the perspective of screening biotherapeutic molecules in mouse models of Parkinson's disease. A preliminary study with a LacZ-encoding vector injected above the substantia nigra of C57BL/6j mice indicated that lentiviral vectors can infect approximately 40,000 cells and diffuse over long distances. Based on these results, glial cell line-derived neurotrophic factor (GDNF) was assessed as a neuroprotective molecule in a 6-hydroxydopamine model of Parkinson's disease. Lentiviral vectors carrying the cDNA for GDNF or mutated GDNF were unilaterally injected above the substantia nigra of C57BL/6j mice. Two weeks later, the animals were lesioned ipsilaterally with 6-hydroxydopamine into the striatum. Apomorphine-induced rotation was significantly decreased in the GDNF-injected group compared to control animals. Moreover, GDNF efficiently protected 69.5% of the tyrosine hydroxylase-positive cells in the substantia nigra against 6-hydroxydopamine-induced toxicity compared to 33.1% with control mutated GDNF. These data indicate that lentiviral vectors constitute a powerful gene delivery system for the screening of therapeutic molecules in mouse models of Parkinson's disease. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/10877911/Lentiviral_vectors_as_a_gene_delivery_system_in_the_mouse_midbrain:_cellular_and_behavioral_improvements_in_a_6_OHDA_model_of_Parkinson's_disease_using_GDNF_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(00)97409-0 DB - PRIME DP - Unbound Medicine ER -