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Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease.
Gene Ther. 2002 Mar; 9(6):381-9.GT

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a strong candidate agent in the neuroprotective treatment of Parkinson's disease (PD). We investigated whether adeno-associated viral (AAV) vector-mediated delivery of a GDNF gene in a delayed manner could prevent progressive degeneration of dopaminergic (DA) neurons, while preserving a functional nigrostriatal pathway. Four weeks after a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), rats received injection of AAV vectors expressing GDNF tagged with FLAG peptide (AAV-GDNFflag) or beta-galactosidase (AAV-LacZ) into the lesioned striatum. Immunostaining for FLAG demonstrated retrograde transport of GDNFflag to the substantia nigra (SN). The density of tyrosine hydroxylase (TH)-positive DA fibers in the striatum and the number of TH-positive or cholera toxin subunit B (CTB, neuronal tracer)-labeled neurons in the SN were significantly greater in the AAV-GDNFflag group than in the AAV-LacZ group. Dopamine levels and those of its metabolites in the striatum were remarkably higher in the AAV-GDNFflag group compared with the control group. Consistent with anatomical and biochemical changes, significant behavioral recovery was observed from 4-20 weeks following AAV-GDNFflag injection. These data indicate that a delayed delivery of GDNF gene using AAV vector is efficacious even 4 weeks after the onset of progressive degeneration in a rat model of PD.

Authors+Show Affiliations

Department of Neurology, Jichi Medical School, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11960314

Citation

Wang, L, et al. "Delayed Delivery of AAV-GDNF Prevents Nigral Neurodegeneration and Promotes Functional Recovery in a Rat Model of Parkinson's Disease." Gene Therapy, vol. 9, no. 6, 2002, pp. 381-9.
Wang L, Muramatsu S, Lu Y, et al. Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. Gene Ther. 2002;9(6):381-9.
Wang, L., Muramatsu, S., Lu, Y., Ikeguchi, K., Fujimoto, K., Okada, T., Mizukami, H., Hanazono, Y., Kume, A., Urano, F., Ichinose, H., Nagatsu, T., Nakano, I., & Ozawa, K. (2002). Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. Gene Therapy, 9(6), 381-9.
Wang L, et al. Delayed Delivery of AAV-GDNF Prevents Nigral Neurodegeneration and Promotes Functional Recovery in a Rat Model of Parkinson's Disease. Gene Ther. 2002;9(6):381-9. PubMed PMID: 11960314.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. AU - Wang,L, AU - Muramatsu,S, AU - Lu,Y, AU - Ikeguchi,K, AU - Fujimoto,K, AU - Okada,T, AU - Mizukami,H, AU - Hanazono,Y, AU - Kume,A, AU - Urano,F, AU - Ichinose,H, AU - Nagatsu,T, AU - Nakano,I, AU - Ozawa,K, PY - 2001/09/12/received PY - 2002/01/23/accepted PY - 2002/4/18/pubmed PY - 2002/5/15/medline PY - 2002/4/18/entrez SP - 381 EP - 9 JF - Gene therapy JO - Gene Ther. VL - 9 IS - 6 N2 - Glial cell line-derived neurotrophic factor (GDNF) is a strong candidate agent in the neuroprotective treatment of Parkinson's disease (PD). We investigated whether adeno-associated viral (AAV) vector-mediated delivery of a GDNF gene in a delayed manner could prevent progressive degeneration of dopaminergic (DA) neurons, while preserving a functional nigrostriatal pathway. Four weeks after a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), rats received injection of AAV vectors expressing GDNF tagged with FLAG peptide (AAV-GDNFflag) or beta-galactosidase (AAV-LacZ) into the lesioned striatum. Immunostaining for FLAG demonstrated retrograde transport of GDNFflag to the substantia nigra (SN). The density of tyrosine hydroxylase (TH)-positive DA fibers in the striatum and the number of TH-positive or cholera toxin subunit B (CTB, neuronal tracer)-labeled neurons in the SN were significantly greater in the AAV-GDNFflag group than in the AAV-LacZ group. Dopamine levels and those of its metabolites in the striatum were remarkably higher in the AAV-GDNFflag group compared with the control group. Consistent with anatomical and biochemical changes, significant behavioral recovery was observed from 4-20 weeks following AAV-GDNFflag injection. These data indicate that a delayed delivery of GDNF gene using AAV vector is efficacious even 4 weeks after the onset of progressive degeneration in a rat model of PD. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/11960314/Delayed_delivery_of_AAV_GDNF_prevents_nigral_neurodegeneration_and_promotes_functional_recovery_in_a_rat_model_of_Parkinson's_disease_ L2 - http://dx.doi.org/10.1038/sj.gt.3301682 DB - PRIME DP - Unbound Medicine ER -