Mouatt-Prigent A, Agid Y, Hirsch E C
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Brain Res. 1994 Dec 30;668(1-2):62-70. doi: 10.1016/0006-8993(94)90511-8.
Parkinson's disease (PD) is characterized by a heterogeneous loss of dopaminergic neurons in the human mesencephalon affecting mainly the substantia nigra pars compacta (SNpc) and to a lesser extent the other dopaminergic cell groups. A rise in intracellular calcium concentrations represents one of the final events leading to nerve cell death. Calbindin D28k, a protein capable of buffering intracellular calcium concentrations is present in the dopaminergic neurons that are selectively preserved in PD but not in those that degenerate. To determine whether other calcium-binding proteins also represent putative protective factors of dopaminergic neurons in PD, we analyzed immunohistochemically the distribution of calretinin-containing (CR+) neurons, in the human mesencephalon of three control subjects and four patients with PD. No significant differences were observed between the number of CR+ neurons in the two subject groups. Sequential double immunostaining for calretinin and tyrosine hydroxylase showed a variable proportion of CR+ neurons among dopaminergic neurons: moderate co-localization was found in catecholaminergic cell group A8 and in the dorsal part of the ventral tegmental area (VTA) and low co-localization in the SNpc, the ventral part of the VTA and the central gray substance. This indicates that calretinin may only protect some dopaminergic neurons against degeneration in PD. Yet, in the SNpc a selective preservation of CR+ dopaminergic neurons was observed, suggesting a neuroprotective role in some dopaminergic cell groups only.
帕金森病（PD）的特征是人类中脑中多巴胺能神经元的异质性丧失，主要影响黑质致密部（SNpc），对其他多巴胺能细胞群的影响较小。细胞内钙浓度升高是导致神经细胞死亡的最终事件之一。钙结合蛋白D28k是一种能够缓冲细胞内钙浓度的蛋白质，存在于PD中选择性保留的多巴胺能神经元中，而不存在于退化的神经元中。为了确定其他钙结合蛋白是否也代表PD中多巴胺能神经元的假定保护因子，我们对三名对照受试者和四名PD患者的人类中脑进行了免疫组织化学分析，以检测含钙视网膜蛋白（CR+）神经元的分布。两组受试者中CR+神经元的数量未观察到显著差异。对钙视网膜蛋白和酪氨酸羟化酶进行连续双重免疫染色显示，多巴胺能神经元中CR+神经元所占比例各不相同：在儿茶酚胺能细胞群A8和腹侧被盖区（VTA）的背侧部分发现中等程度的共定位，而在SNpc、VTA的腹侧部分和中央灰质中发现低共定位。这表明钙视网膜蛋白可能仅保护某些多巴胺能神经元免于在PD中退化。然而，在SNpc中观察到CR+多巴胺能神经元的选择性保留，表明其仅在某些多巴胺能细胞群中具有神经保护作用。
