6-HYDROXYDOPAMINE LESION OF THE RAT SUBSTANTIA-NIGRA - TIME-COURSE AND MORPHOLOGY OF CELL-DEATH
6-HYDROXYDOPAMINE LESION OF THE RAT SUBSTANTIA-NIGRA - TIME-COURSE AND MORPHOLOGY OF CELL-DEATH
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DOI：
10.1006/neur.1995.0016
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发表时间：
1995-06-01
期刊：
影响因子：
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通讯作者：
BURKE, RE
中科院分区：
文献类型：
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作者：
JEON, BS;JACKSONLEWIS, V;BURKE, RE
大鼠黑质损伤的6-羟基多巴胺（6-OHDA）模型多年来一直被用作帕金森综合征的标准动物模型。虽然早期的研究建立了在细胞体和终端的儿茶酚胺组织荧光或酪氨酸羟化酶免疫染色的损失的时间过程中，这些表型表达的改变不定义的时间过程中的形态学变性。因此，我们使用了银浸渍方法来表征黑质纹状体系统神经元变性的时间过程和形态。早在黑质6-OHDA注射后12小时，在纹状体终末变性的任何证据之前，就在黑质丘脑部（SNpc）中观察到大量神经元死亡。从1到7天的神经元死亡伴随着纹状体纤维变性。7天后，不再看到纤维变性，但可识别的神经元死亡持续低水平长达31天，染色的无定形物质存在于60天。早期细胞死亡的形态学模式与晚期相似，包括胞质银沉积和核仁深染。在任何时候都没有观察到细胞凋亡的形态。我们的结论是，神经元死亡是一个渐进的过程后，6-OHDA损伤，在整个变性过程中具有相似的形态。
The 6-hydroxydopamine (6-OHDA) model of nigral injury in rats has been in use as a standard animal model of parkinsonism for many years. While earlier studies established the time course for loss of catecholamine histofluorescence or tyrosine hydroxylase immunostaining in the cell bodies and terminals, these alterations in phenotypic expression do not define the time course of morphologic degeneration. We have therefore used a silver impregnation method to characterize the time course and morphology of the degeneration of neurons in the nigrostriatal system. Abundant neuronal death was observed in substantia nigra pars compacta (SNpc) as early as 12 hours after nigral 6-OHDA injection, and prior to any evidence of striatal terminal degeneration. From 1 to 7 days neuron death was accompanied by striatal fibre degeneration. After 7 days, fibre degeneration was no longer seen, but identifiable neuron death continued at low levels for as long as 31 days, and stained amorphous material was present at 60 days. The morphologic pattern of cell death in the early phase was similar to that in the late phase, and included cytoplasmic silver deposits and dark staining of the nucleolus. At no time was the morphology of apoptosis observed. We conclude that neuron death is a progressive process following 6-OHDA lesion, with similar morphology throughout the course of degeneration.