Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector
Neuroprotection in the rat Parkinson model by intrastriatal GDNF gene transfer using a lentiviral vector
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DOI：
10.1097/00001756-200201210-00019
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发表时间：
2002-01-21
期刊：
影响因子：
1.7
通讯作者：
Björklund, A
中科院分区：
文献类型：
--
作者：
Georgievska, B;Kirik, D;Björklund, A
我们使用重组慢病毒载体（rLV）将GDNF基因递送到纹状体，并评估其在纹状体内6-羟基多巴胺（6-OHDA）损伤模型中的神经保护作用。用rLV-GDNF载体获得的GDNF表达水平是剂量相关的，并且在转导的纹状体中范围在0.9- 9.3ng/mg组织之间，如通过ELISA测定的，并且由于GDNF蛋白的顺行转运，在同侧黑质（SN）中检测到0.2- 3.0ng/mg组织。GDNF表达在注射后4天明显，并维持大于或等于8个月。纹状体递送rLV-GDNF有效地保护黑质多巴胺（DA）神经元及其投射，对抗6-OHDA损伤（65-77%的完整侧）。沿着黑质纹状体通路观察到损伤轴突的发芽，精确地对应于含有顺行运输的GDNF NeuroReport 13：75-82（C）2002 Lippincott威廉姆斯Wilkins的区域。
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.