Functional reinnervation from remaining DA terminals induced by GDNF lentivirus in a rat model of early Parkinson's disease
Functional reinnervation from remaining DA terminals induced by GDNF lentivirus in a rat model of early Parkinson's disease
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DOI：
10.1016/j.nbd.2005.06.015
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发表时间：
2006-01-01
影响因子：
6.1
通讯作者：
Savasta, M
中科院分区：
文献类型：
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作者：
Brizard, M;Carcenac, C;Savasta, M
神经胶质细胞系衍生神经营养因子（GDNF）是恢复多巴胺（DA）黑质纹状体系统功能神经再生和/或神经保护，从而治疗帕金森病（PD）的良好候选药物。病毒递送是目前最有可能将治疗性蛋白递送到大脑以治疗神经系统疾病的体内策略。然而，该策略尚未解决的一个重要问题是，从GDNF治疗中获得最佳益处所必需的DA黑质神经元和/或纹状体DA终端的阈值数量。在这项研究中，我们在一个新的早期帕金森病大鼠模型中使用慢病毒载体检测了长期GDNF给药的纹间质神经营养效应。在部分黑质致密部6-羟多巴胺损伤后4周，将lentigdnf注射到纹状体。通过酪氨酸羟酶阳性DA纤维密度评估纹状体失神经支配，并通过楼梯试验测试运动缺陷来证实。GDNF治疗恢复了以前失神经区纹状体DA神经的完全支配，这与显著的行为改善有关。(c) 2005爱思唯尔公司版权所有。
Glial cell-line derived neurotrophic factor (GDNF) is a good candidate agent for restoring functional reinnervation and/or neuroprotection of dopamine (DA) nigrostriatal system and thus for the treatment of Parkinson's disease (PD). Viral delivery is currently the most likely in vivo strategy for delivery of the therapeutic protein into the brain for treatment of neurological diseases. However, one of the important unresolved issues for this strategy is the threshold number of DA nigral neurons and/or of striatal DA terminals necessary for optimal benefit from GDNF therapy. In this study, we examined the intrastriatal neurotrophic effects of long-term GDNF delivery using a lentiviral vector in a new rat model of early PD. Lenti-GDNF was injected into the striatum 4 weeks after partial substantia nigra pars compacta 6-hydroxydopamine-induced lesion. Striatal denervation was evaluated by assessing tyrosine hydroxylase-positive DA fiber density and corroborated by testing motor deficit by means of a staircase test. GDNF treatment restored complete striatal DA innervation in the previously denervated area and this was associated with significant behavioral improvements. (c) 2005 Elsevier Inc. All rights reserved.