Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector
- 1 January 2002
- journal article
- regeneration and-transplantation
- Published by Wolters Kluwer Health in NeuroReport
- Vol. 13 (1) , 75-82
- https://doi.org/10.1097/00001756-200201210-00019
Abstract
We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model. The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9–9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2–3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for ≥ 8 months after injection. Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65–77% of intact side). Sprouting of the lesioned axons was observed along the nigrostriatal pathway, precisely corresponding to the areas containing anterogradely transported GDNF.Keywords
This publication has 20 references indexed in Scilit:
- Preservation of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6‐OHDA lesion model depends on the site of administration of the trophic factorEuropean Journal of Neuroscience, 2000
- Neurodegeneration Prevented by Lentiviral Vector Delivery of GDNF in Primate Models of Parkinson's DiseaseScience, 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 GDNFExperimental Neurology, 2000
- Long-Term rAAV-Mediated Gene Transfer of GDNF in the Rat Parkinson's Model: Intrastriatal But Not Intranigral Transduction Promotes Functional Regeneration in the Lesioned Nigrostriatal SystemJournal of Neuroscience, 2000
- In Vivo Protection of Nigral Dopamine Neurons by Lentiviral Gene Transfer of the Novel GDNF-Family Member Neublastin/ArteminMolecular and Cellular Neuroscience, 2000
- Sequential Administration of GDNF into the Substantia Nigra and Striatum Promotes Dopamine Neuron Survival and Axonal Sprouting but Not Striatal Reinnervation or Functional Recovery in the Partial 6-OHDA Lesion ModelExperimental Neurology, 2000
- Self-Inactivating Lentiviral Vectors with Enhanced Transgene Expression as Potential Gene Transfer System in Parkinson's DiseaseHuman Gene Therapy, 2000
- Lentiviral Gene Transfer to the Nonhuman Primate BrainExperimental Neurology, 1999
- Short-Term GDNF Treatment Provides Long-Term Rescue of Lesioned Nigral Dopaminergic Neurons in a Rat Model of Parkinson’s DiseaseJournal of Neuroscience, 1996
- In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral VectorScience, 1996