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Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson's disease.
Exp Neurol. 1999 Nov; 160(1):205-14.EN

Abstract

Previous work has demonstrated that viral vector mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF), when administered prior to a striatal injection of the specific neurotoxin, 6-hydroxydopamine (6-OHDA), can protect nigral dopamine (DA) neurons from cell death. When considering gene therapy for Parkinson's disease (PD), vector delivery prior to the onset of neuropathology is not possible and chronic delivery will likely be necessary in a GDNF-based PD therapy. The present study was undertaken to determine if GDNF delivered via a recombinant adeno-associated viral vector (rAAV) could affect nigral DA cell survival when initiated just after the administration of striatal 6-OHDA. The onset of rAAV-mediated GDNF transgene expression near the substantia nigra was determined to begin somewhere between 1 and 7 days after the 6-OHDA injection and subsequent vector administration. The cell survival data indicate that rAAV-GDNF delivery results in a highly significant sparing of nigral DA neurons. These data indicate that a single delivery of rAAV encoding GDNF is efficacious when delivered after the onset of progressive degeneration in a rat model of PD.

Authors+Show Affiliations

Department of Neuroscience, University of Florida Brain Institute, University of Florida College of Medicine, Gainesville 32610-0244, USA. rmandel@ufbi.ufl.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10630205

Citation

Mandel, R J., et al. "Recombinant Adeno-associated Viral Vector-mediated Glial Cell Line-derived Neurotrophic Factor Gene Transfer Protects Nigral Dopamine Neurons After Onset of Progressive Degeneration in a Rat Model of Parkinson's Disease." Experimental Neurology, vol. 160, no. 1, 1999, pp. 205-14.
Mandel RJ, Snyder RO, Leff SE. Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson's disease. Exp Neurol. 1999;160(1):205-14.
Mandel, R. J., Snyder, R. O., & Leff, S. E. (1999). Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson's disease. Experimental Neurology, 160(1), 205-14.
Mandel RJ, Snyder RO, Leff SE. Recombinant Adeno-associated Viral Vector-mediated Glial Cell Line-derived Neurotrophic Factor Gene Transfer Protects Nigral Dopamine Neurons After Onset of Progressive Degeneration in a Rat Model of Parkinson's Disease. Exp Neurol. 1999;160(1):205-14. PubMed PMID: 10630205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant adeno-associated viral vector-mediated glial cell line-derived neurotrophic factor gene transfer protects nigral dopamine neurons after onset of progressive degeneration in a rat model of Parkinson's disease. AU - Mandel,R J, AU - Snyder,R O, AU - Leff,S E, PY - 2000/1/12/pubmed PY - 2000/1/12/medline PY - 2000/1/12/entrez SP - 205 EP - 14 JF - Experimental neurology JO - Exp Neurol VL - 160 IS - 1 N2 - Previous work has demonstrated that viral vector mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF), when administered prior to a striatal injection of the specific neurotoxin, 6-hydroxydopamine (6-OHDA), can protect nigral dopamine (DA) neurons from cell death. When considering gene therapy for Parkinson's disease (PD), vector delivery prior to the onset of neuropathology is not possible and chronic delivery will likely be necessary in a GDNF-based PD therapy. The present study was undertaken to determine if GDNF delivered via a recombinant adeno-associated viral vector (rAAV) could affect nigral DA cell survival when initiated just after the administration of striatal 6-OHDA. The onset of rAAV-mediated GDNF transgene expression near the substantia nigra was determined to begin somewhere between 1 and 7 days after the 6-OHDA injection and subsequent vector administration. The cell survival data indicate that rAAV-GDNF delivery results in a highly significant sparing of nigral DA neurons. These data indicate that a single delivery of rAAV encoding GDNF is efficacious when delivered after the onset of progressive degeneration in a rat model of PD. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/10630205/Recombinant_adeno_associated_viral_vector_mediated_glial_cell_line_derived_neurotrophic_factor_gene_transfer_protects_nigral_dopamine_neurons_after_onset_of_progressive_degeneration_in_a_rat_model_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(99)97203-5 DB - PRIME DP - Unbound Medicine ER -