Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector

被引:113
作者
Georgievska, B [1 ]
Kirik, D [1 ]
Rosenblad, C [1 ]
Lundberg, C [1 ]
Björklund, A [1 ]
机构
[1] Lund Univ, Dept Physiol Sci, Wallenberg Neurosci Ctr, S-22184 Lund, Sweden
关键词
behavior; cell counts; dopamine; glial cell line-derived neurotrophic factor; 6-hydroxydopamine; lentiviral vector; neuroprotection; Parkinson's disease; sprouting; tyrosine hydroxylase;
D O I
10.1097/00001756-200201210-00019
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
We used a recombinant lentiviral vector (rLV) for gene delivery of GDNF to the striatum, and assessed its neuroprotective effects in the intrastriatal 6-hydroxydopamine (6-OHDA) lesion model. The level of GDNF expression obtained with the rLV-GDNF vector was dose-related and ranged between 0.9-9.3 ng/mg tissue in the transduced striatum, as determined by ELISA, and 0.2-3.0 ng/mg tissue were detected in the ipsilateral substantia nigra (SN), due to anterograde transport of the GDNF protein. GDNF expression was apparent at 4 days and maintained for greater than or equal to8 months after injection, Striatal delivery of rLV-GDNF efficiently protected the nigral dopamine (DA) neurons and their projection, against the 6-OHDA lesion (65-77% of intact side). Sprouting of the lesioned axons was observed along the nigrostriatal pathway, precisely corresponding to the areas containing anterogradely transported GDNF NeuroReport 13:75-82 (C) 2002 Lippincott Williams Wilkins.
引用
收藏
页码:75 / 82
页数:8
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