Intrastriatal gene transfer of vascular endothelial growth factor rescues dopaminergic neurons in a rat Parkinson's disease model

被引:3
作者
Tian Y. [1 ]
Sun S. [1 ]
Tang C. [1 ]
Wang J. [1 ]
Chen X. [1 ]
Qiao X. [1 ]
机构
[1] Department of Neurology, Union Hospital, Tongji Medical College
来源
Journal of Huazhong University of Science and Technology | 2006年 / 26卷 / 6期
关键词
vascular endothelial growth factor A; Parkinson’s disease; gene therapy; gene transfer technique;
D O I
10.1007/s11596-006-0611-7
中图分类号
学科分类号
摘要
To examine the ability of intrastriatal gene transfer of vascular endothelial growth factor 165 mediated by adenoviral vector to rescue dopaminergic neurons in a rat model of Parkinson's disease (PD), we constructed recombinant replication-deficient adenoviral vectors carrying the gene of VEGF165 (Ad-VEGF), and injected Ad-VEGF (or Ad-LacZ and PBS as controls) into the striatum of rats 7 days after the lesion by 6-hydroxydopamine. The rat rotational behavior analysis and tyrosine hydroxylase (TH) immunohistochemistry were performed to assess the change of dopaminergic neurons. Our results showed that the rats receiving Ad-VEGF injection displayed a significant improvement in apomorphine-induced rotational behavior and a significant preservation of TH-positive neurons and fibers compared with control animals. It is concluded that intrastriatal gene transfer by Ad-VEGF may rescue the dopaminergic neurons from degeneration in a rat model of PD.
引用
收藏
页码:670 / 673
页数:3
相关论文
共 26 条
[1]  
Storkebaum E.(2004)VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection Bioessays 26 943-954
[2]  
Lambrechts D.(2004)VEGF: a critical player in neurodegeneration J Clin Invest 113 14-18
[3]  
Carmeliet P.(2002)Construction and characterization of replication-deficient adenvoiral vector encoding for human vascular endothelial growth factor 165 Chin J of Clin Lab Sci (Chin) 20 156-158
[4]  
Storkebaum E.(1995)Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine Neuroscience 67 631-647
[5]  
Carmeliet P.(1993)Correlation of apomorphine-and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxy-dopamine lesioned rats Brain Res 626 167-174
[6]  
Wang C. Q.(2001)Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity: signal transduction cascades FASEB J 15 1218-1220
[7]  
Wang J. N.(2002)Vascular endothelial growth factor protects cultured rat hippocampal neurons against hypoxic injury via an antiexcitotoxic, caspase-independent mechanism J Cereb Blood Flow Metab 22 1170-1175
[8]  
Huang Y. Z.(2004)Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease Eur J Neurosci 19 1494-1504
[9]  
Przedborski S.(2000)Neurodegeneration Prevented by Lentiviral Vector Delivery of GDNF in Primate Models of Parkinson’s Disease Science 290 767-773
[10]  
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