Favorable effects of VEGF gene transfer on a rat model of Parkinson disease using adeno-associated viral vectors.
Vascular endothelial growth factor (VEGF) is a specific angiogenic peptide, which has been identified to play a critical role in neurodegeneration, and has beneficial effects on neurons. In this study, we investigated whether neurodegeneration in a rat model of Parkinson disease could be prevented by VEGF gene transfer mediated by adeno-associated virus (AAV) vectors. Our results demonstrated that a single injection of a VEGF-expressing AAV vector into striatum improved the rotational behavior of rat Parkinson disease models, and promoted the survival of dopaminergic neurons and fibers. Meanwhile, AAV-VEGF injection significantly increased the reactive astrocytes and the levels of glial cell line-derived neurotrophic factor in striatum, but did not induce extra angiogenesis and remarkable disorder of blood-brain barrier. We thus conclude that intrastriatal delivery of VEGF gene mediated by AAV has favorable effects on the dopaminergic neurons in a rat Parkinson disease model.
Tian
You-yong
YY
Department of Neurology, The Affiliated Union Hospital of Huazhong University of Science & Technology, Wuhan 430022, PR China.
Tang
Cui-Ju
CJ
Wang
Jia-ning
JN
Feng
Yuan
Y
Chen
Xiao-wu
XW
Wang
Lan
L
Qiao
Xian
X
Sun
Sheng-gang
SG
D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D049109:Cell Proliferation; D000229:Dependovirus / Q000502:physiology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D016716:PC12 Cells / Q000502:physiology; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test / Q000379:methods; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000502:physiology*
D018663:Adrenergic Agents; D042461:Vascular Endothelial Growth Factor A; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase