Does monoamine oxidase type B play a role in dopaminergic nerve cell death in Parkinson's disease?
Does monoamine oxidase type B play a role in dopaminergic nerve cell death in Parkinson's disease?
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DOI：
10.1212/wnl.46.5.1262
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发表时间：
1996-05-01
期刊：
影响因子：
9.9
通讯作者：
Hirsch, EC
中科院分区：
文献类型：
--
作者：
Damier, P;Kastner, A;Hirsch, EC
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。单胺氧化酶B型（MAO-B）催化多巴胺的氧化降解产生自由基，因此可能与变性过程有关。为此，我们通过免疫组织化学方法研究了5例PD患者和5例对照组中脑含MAO-B细胞的分布。MAO-B样免疫反应在胶质细胞，纤维和神经元中检测到。虽然大多数的MAO-B阳性神经元可能属于中缝背侧，我们证明了双标记免疫组织化学，其中一些也多巴胺能。MAO-B阳性多巴胺能神经元存在于对照中脑的所有多巴胺能组中。在黑质内，大多数多巴胺能神经元位于背侧部分的结构。在PD中脑中仍然检测到MAO-B阳性多巴胺能神经元。与对照组相比，含有MAO-B的多巴胺能神经元的损失（-45%）并不高于MAO-B阴性的多巴胺能神经元的损失（-59%）。MAO-B阳性神经胶质细胞的密度在对照中脑中变化：在受影响最小的多巴胺能组（中央灰质）中高，在受影响最大的区域（黑质部）中低。对照中脑多巴胺能细胞亚群中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）。我们的结论是，单胺氧化酶-B在多巴胺神经元的存在并不有助于脆弱性PD。此外，它在某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。
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.