Hirsch E C
INSERM U 289, Hôpital de la Salpêtrière, Paris, France.
Mol Neurobiol. 1994 Aug-Dec;9(1-3):135-42. doi: 10.1007/BF02816113.
The cardinal neurochemical abnormality in Parkinson's disease is the decreased dopamine content in the striatum, resulting from the loss of dopaminergic neurons in the mesencephalon. Precise analysis of the dopaminergic neurons in the midbrain demonstrates, however, that this cell loss is not uniform. Some dopaminergic cell groups are more vulnerable than others. The degree of cell loss is severe in the substantia nigra pars compacta, intermediate in the ventral tegmental area and cell group A8, but nonexistent in the central gray substance. This heterogeneity provides a good paradigm for analyzing the factors implicated in this differential vulnerability. So far, the neurons that degenerate have been shown to contain neuromelanin, high amounts of iron, and no calbindin28K, and to be poorly protected against oxidative stress. By contrast, the neurons that survive in Parkinson's disease are free of neuromelanin, calbindinD28-positive, contain low amounts of iron, and are better protected against oxidative stress. The analysis of the pattern of cell loss in Parkinson's disease may thus bring new clues as to the mechanism of nerve cell death in Parkinson's disease.
帕金森病主要的神经化学异常是纹状体中多巴胺含量降低，这是由于中脑多巴胺能神经元缺失所致。然而，对中脑多巴胺能神经元的精确分析表明，这种细胞缺失并不均匀。一些多巴胺能细胞群比其他细胞群更易受损。致密部黑质的细胞缺失程度严重，腹侧被盖区和A8细胞群的细胞缺失程度中等，而中央灰质中则不存在细胞缺失。这种异质性为分析导致这种差异易损性的因素提供了一个很好的范例。到目前为止，已证实退化的神经元含有神经黑色素、大量铁且无钙结合蛋白28K，并且对氧化应激的保护作用较弱。相比之下，帕金森病中存活的神经元不含神经黑色素，钙结合蛋白D28呈阳性，含铁量低，并且对氧化应激的保护作用更好。因此，对帕金森病细胞缺失模式的分析可能会为帕金森病神经细胞死亡机制带来新线索。
