Jeon B S, Jackson-Lewis V, Burke R E
Department of Neurology, Seoul National University Hospital, Korea.
Neurodegeneration. 1995 Jun;4(2):131-7. doi: 10.1006/neur.1995.0016.
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.
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病的标准动物模型。虽然早期研究确定了细胞体和终末中儿茶酚胺组织荧光或酪氨酸羟化酶免疫染色丧失的时间进程，但这些表型表达的改变并未界定形态学退变的时间进程。因此，我们采用银浸染法来描述黑质纹状体系统中神经元退变的时间进程和形态学特征。早在黑质注射6-OHDA后12小时，在黑质致密部（SNpc）就观察到大量神经元死亡，且早于纹状体终末退变的任何迹象。在1至7天，神经元死亡伴随着纹状体纤维退变。7天后，不再见到纤维退变，但可识别的神经元死亡持续低水平达31天，且在60天时存在染色的无定形物质。早期细胞死亡的形态学模式与晚期相似，包括细胞质银沉积和核仁深染。在任何时候均未观察到凋亡形态。我们得出结论，6-OHDA损伤后神经元死亡是一个渐进过程，在整个退变过程中形态相似。
