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Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease.
Brain Res Mol Brain Res. 2005 Mar 24; 134(1):155-61.BR

Abstract

Gene transfer of glial cell line-derived neurotrophic factor (GDNF) in rodent models of Parkinson's disease (PD) has been shown to protect against neurodegeneration either prior to or immediately after neurotoxin-induced lesions; however, the nigrostriatal pathway was largely intact when gene delivery was completed in these models, which may not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, replication-incompetent adenoviral vectors encoding the rat GDNF gene were administered into the striatum 4 weeks following 6-hydroxydopamine (6-OHDA) injection in the unilateral striatum, more closely resembling fully developed PD. Apomorphine-induced rotational behavior testing was performed every week following 6-OHDA injection. At the 10th week after gene transfer, the striatal dopamine concentrations were measured by HPLC with an electrochemical detector and the number of tyrosine hydroxylase (TH)-positive dopamine neurons in the substantia nigra (SN) was determined by immunohistochemistry. Injection of 6-OHDA into the striatum produced stable increases in rotation, which reached a plateau between 4 and 5 weeks post-injection. The number of TH-positive neuron in the SN and dopamine levels in the striatum was significantly lower in the 6-OHDA group compared to the normal group. Gene transfer of GDNF, but not beta-galactosidase, significantly increased the number of TH-positive neurons and dopamine levels, with a subsequent behavioral recovery between 5 and 10 weeks following GDNF transduction. These findings demonstrate that adenovirus-mediated gene transfer of GDNF is efficacious even in the late stages of 6-OHDA-induced PD rats. They also provide further evidence on the effectiveness of GDNF-based gene therapy for experimental Parkinson's disease.

Authors+Show Affiliations

Department of Neurosurgery, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310003, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15790539

Citation

Zheng, Jie-Sheng, et al. "Delayed Gene Therapy of Glial Cell Line-derived Neurotrophic Factor Is Efficacious in a Rat Model of Parkinson's Disease." Brain Research. Molecular Brain Research, vol. 134, no. 1, 2005, pp. 155-61.
Zheng JS, Tang LL, Zheng SS, et al. Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease. Brain Res Mol Brain Res. 2005;134(1):155-61.
Zheng, J. S., Tang, L. L., Zheng, S. S., Zhan, R. Y., Zhou, Y. Q., Goudreau, J., Kaufman, D., & Chen, A. F. (2005). Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease. Brain Research. Molecular Brain Research, 134(1), 155-61.
Zheng JS, et al. Delayed Gene Therapy of Glial Cell Line-derived Neurotrophic Factor Is Efficacious in a Rat Model of Parkinson's Disease. Brain Res Mol Brain Res. 2005 Mar 24;134(1):155-61. PubMed PMID: 15790539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease. AU - Zheng,Jie-Sheng, AU - Tang,Ling-Ling, AU - Zheng,Shu-Sen, AU - Zhan,Ren-Ya, AU - Zhou,Yong-Qing, AU - Goudreau,John, AU - Kaufman,David, AU - Chen,Alex F, PY - 2004/06/22/accepted PY - 2005/3/26/pubmed PY - 2005/6/14/medline PY - 2005/3/26/entrez SP - 155 EP - 61 JF - Brain research. Molecular brain research JO - Brain Res Mol Brain Res VL - 134 IS - 1 N2 - Gene transfer of glial cell line-derived neurotrophic factor (GDNF) in rodent models of Parkinson's disease (PD) has been shown to protect against neurodegeneration either prior to or immediately after neurotoxin-induced lesions; however, the nigrostriatal pathway was largely intact when gene delivery was completed in these models, which may not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, replication-incompetent adenoviral vectors encoding the rat GDNF gene were administered into the striatum 4 weeks following 6-hydroxydopamine (6-OHDA) injection in the unilateral striatum, more closely resembling fully developed PD. Apomorphine-induced rotational behavior testing was performed every week following 6-OHDA injection. At the 10th week after gene transfer, the striatal dopamine concentrations were measured by HPLC with an electrochemical detector and the number of tyrosine hydroxylase (TH)-positive dopamine neurons in the substantia nigra (SN) was determined by immunohistochemistry. Injection of 6-OHDA into the striatum produced stable increases in rotation, which reached a plateau between 4 and 5 weeks post-injection. The number of TH-positive neuron in the SN and dopamine levels in the striatum was significantly lower in the 6-OHDA group compared to the normal group. Gene transfer of GDNF, but not beta-galactosidase, significantly increased the number of TH-positive neurons and dopamine levels, with a subsequent behavioral recovery between 5 and 10 weeks following GDNF transduction. These findings demonstrate that adenovirus-mediated gene transfer of GDNF is efficacious even in the late stages of 6-OHDA-induced PD rats. They also provide further evidence on the effectiveness of GDNF-based gene therapy for experimental Parkinson's disease. SN - 0169-328X UR - https://www.unboundmedicine.com/medline/citation/15790539/Delayed_gene_therapy_of_glial_cell_line_derived_neurotrophic_factor_is_efficacious_in_a_rat_model_of_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -