Kastner A, Hirsch E C, Lejeune O, Javoy-Agid F, Rascol O, Agid Y
INSERM U. 289, Hôpital de la Salpêtrière, Paris, France.
J Neurochem. 1992 Sep;59(3):1080-9. doi: 10.1111/j.1471-4159.1992.tb08350.x.
The contribution of neuromelanin (NM) to the pathogenesis of Parkinson's disease (PD) has long been suspected. In particular, a correlation has been reported between the estimated cell loss in the mesencephalic dopaminergic cell groups and the percentage of NM-pigmented neurons in these cell groups. To test whether the amount of pigment per cell is a critical factor or whether the presence of NM within a neuron is sufficient to account for the degeneration of dopaminergic neurons, the NM content was measured in each neuron from representative sections throughout the ventral mesencephalon of four controls subjects and four patients with PD. Intraneuronal NM was quantified by a densitometric method, using known amounts of synthetic melanin as standards. In control brains, the distribution of melanized neurons in the nigral complex showed a high proportion of lightly melanized neurons in the ventral tegmental area and the pars alpha and gamma of the substantia nigra (SN), whereas heavily melanized neurons were mostly located in the pars beta and lateralis of the SN. An inverse relationship was observed between the percentage of surviving neurons in PD compared with controls and the amount of NM they contain, suggesting that the vulnerability of the dopaminergic neurons is related to their NM content. Factors other than NM may be involved in the differential vulnerability of catecholaminergic neurons in PD. In particular, the constant topography of the cell loss suggests that cell position within the nigral complex is a key factor.
长期以来，人们一直怀疑神经黑色素（NM）在帕金森病（PD）发病机制中的作用。特别是，有报道称中脑多巴胺能细胞群中估计的细胞损失与这些细胞群中NM色素沉着神经元的百分比之间存在相关性。为了测试每个细胞的色素含量是否是一个关键因素，或者神经元内NM的存在是否足以解释多巴胺能神经元的退化，对4名对照受试者和4名PD患者腹侧中脑代表性切片中的每个神经元的NM含量进行了测量。使用已知量的合成黑色素作为标准，通过密度测定法对神经元内的NM进行定量。在对照大脑中，黑质复合体中黑色素化神经元的分布显示，腹侧被盖区以及黑质（SN）的α和γ部中轻度黑色素化神经元的比例较高，而重度黑色素化神经元大多位于SN的β部和外侧部。观察到与对照相比，PD中存活神经元的百分比与其所含NM量之间呈负相关，这表明多巴胺能神经元的易损性与其NM含量有关。NM以外的因素可能参与了PD中儿茶酚胺能神经元的不同易损性。特别是，细胞损失的恒定地形表明黑质复合体内的细胞位置是一个关键因素。
