Damier P, Kastner A, Agid Y, Hirsch E C
INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Neurology. 1996 May;46(5):1262-9. doi: 10.1212/wnl.46.5.1262.
Evidence supports the role of hyperoxidation phenomena in the mechanism of nerve cell death in Parkinson's disease (PD). The oxidative degradation of dopamine, catalyzed by monoamine oxidase type B (MAO-B), produces free radicals and thus could be implicated in the degenerative process. For this reason, we investigated by immunohistochemistry the distribution of MAO-B-containing cells in the midbrain of five patients with PD and five matched control subjects. MAO-B-like immunoreactivity was detected in glial cells, fibers, and neurons. Although most of the MAO-B-positive neurons probably belonged to the raphe dorsalis, we demonstrated by double-labeling immunohistochemistry that some of them were also dopaminergic. MAO-B-positive dopaminergic neurons were present in all dopaminergic groups of the control midbrain. Within the substantia nigra pars compacta, most dopaminergic neurons were located in the dorsal part of the structure. MAO-B-positive dopaminergic neurons were still detected in PD midbrains. Compared with control subjects, the loss of dopaminergic neurons containing MAO-B (-45%) was no higher than that of MAO-B-negative dopaminergic neurons (-59%). The density of MAO-B-positive glial cells varied in the control midbrains: high in the least affected dopaminergic group (the central gray substance) and low in the most affected region (the substantia nigra pars compacta). The density of MAO-B-positive glial cells within dopaminergic cell subgroups in control midbrains were negatively correlated (r = -0.94; p < 0.02) to the estimated neuronal loss in PD. We conclude that the presence of MAO-B in dopamine-containing neurons does not contribute to vulnerability in PD. Moreover, its presence in some glial cells might have a protective effect against oxidative stress induced by dopamine metabolism.
有证据支持过氧化现象在帕金森病(PD)神经细胞死亡机制中的作用。由B型单胺氧化酶(MAO-B)催化的多巴胺氧化降解会产生自由基,因此可能与退变过程有关。基于此,我们通过免疫组织化学研究了5例PD患者和5例匹配对照者中脑含MAO-B细胞的分布。在胶质细胞、纤维和神经元中检测到了MAO-B样免疫反应性。虽然大多数MAO-B阳性神经元可能属于背侧中缝核,但我们通过双重标记免疫组织化学证明其中一些也是多巴胺能的。对照中脑的所有多巴胺能组中均存在MAO-B阳性多巴胺能神经元。在黑质致密部内,大多数多巴胺能神经元位于该结构的背侧部分。在PD中脑中仍可检测到MAO-B阳性多巴胺能神经元。与对照者相比,含MAO-B的多巴胺能神经元的损失率(-45%)并不高于MAO-B阴性多巴胺能神经元的损失率(-59%)。对照中脑中MAO-B阳性胶质细胞的密度各不相同:在受影响最小的多巴胺能组(中央灰质)中较高,而在受影响最大的区域(黑质致密部)中较低。对照中脑多巴胺能细胞亚组内MAO-B阳性胶质细胞的密度与PD中估计的神经元损失呈负相关(r = -0.94;p < 0.02)。我们得出结论,含多巴胺的神经元中MAO-B的存在并不会导致PD中的易损性。此外,它在一些胶质细胞中的存在可能对多巴胺代谢诱导的氧化应激具有保护作用。