Behavioral improvement and dopamine release in a Parkinsonian rat model.
Behavioral improvement and dopamine release in a Parkinsonian rat model.
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帕金森病大鼠模型的行为改善和多巴胺释放。
DOI：
10.1016/s0304-3940(02)00672-9
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发表时间：
2002
影响因子：
2.5
通讯作者：
Gerin,Christine
中科院分区：
文献类型：
--
作者：
Gerin,Christine
胶质细胞源性神经营养因子（GDNF）基因治疗可能为帕金森病（PD）的治疗提供新的策略。GDNF是一种有效的多巴胺能神经营养因子。GDNF基因治疗的效果通过解剖学、行为学和神经化学方法进行评估。我们研究了通过递送编码人GDNF的腺病毒载体（Ad-）（Ad-GDNF）实现的纹状体GDNF水平增加的保护作用。在纹状体损伤前注射Ad-GDNF。微透析法测定纹状体DA含量。接受6-羟基多巴胺（6-OHDA）的动物只显示出显着减少旋转时相比，接受Ad-GDNF之前的6-OHDA神经毒素。在基础条件下，Ad-GDNF组与6-OHDA组相比，DA浓度显著增加（P≤0.05）（1880%）。Ad-GDNF组与6-OHDA组相比，苯丙胺刺激诱导的DA释放量显著增加（P≤0.05）。这些发现表明，GDNF蛋白在纹状体中的长期递送提供了显著的细胞、行为和神经化学保护。
Glial cell-line derived neurotrophic factor (GDNF) gene therapy might offer new strategies for the treatment of Parkinson's disease (PD). GDNF is a potent dopaminergic (DA) neurotrophic factor. The effect of GDNF gene therapy was assessed using anatomical, behavioral, and neurochemical approaches. We examined the protective effect of increased striatal GDNF levels achieved by delivery of an adenoviral vector (Ad-) encoding human GDNF (Ad-GDNF). Animals were injected with Ad-GDNF prior to striatal lesion. Striatal DA concentration was measured by microdialysis. Animals receiving 6-hydroxydopamine (6-OHDA) only showed a significant decrease in rotation when compared to those receiving Ad-GDNF prior to the 6-OHDA neurotoxin. Under basal conditions, the Ad-GDNF group showed a significant (P≤0.05) increase (1880%) in DA concentration when compared to the 6-OHDA group. Amphetamine challenge induced a significantly (P≤0.05) higher release of DA in the Ad-GDNF group than in the 6-OHDA group. These findings show that long-term delivery of GDNF protein in the striatum provides significant cell, behavioral, and neurochemical protection.