α-Synuclein pathology in the neostriatum in Parkinson’s disease

α-Synuclein pathology in the neostriatum in Parkinson’s disease
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DOI:
10.1007/s00401-007-0316-4
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发表时间:
2008-04
影响因子:
12.7
通讯作者:
F. Mori;K. Tanji;Hai-xin Zhang;A. Kakita;H. Takahashi;K. Wakabayashi
F. Mori;K. Tanji;Hai-xin Zhang;A. Kakita;H. Takahashi;K. Wakabayashi
中科院分区:
医学1区
文献类型:
--
作者:
F. Mori;K. Tanji;Hai-xin Zhang;A. Kakita;H. Takahashi;K. Wakabayashi

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应用抗磷酸化α-突触核蛋白(αS)抗体,对25例有不同程度路易小体病变的有症状和症状前帕金森病(PD)患者的新纹状体进行免疫组织化学检测。这些患者根据Braak等人提出的PD分期进行分类。(Neurobiol Ageing 24:197-211,2003):II期(αS的病理局限于延髓和桥脑被盖),III期(αS的病理学局限于脑干),IV期(边缘期),V期和VI期(新皮质期)。αS免疫组织化学显示新纹状体内有神经元和胶质细胞胞浆内包涵体及神经元性改变。αS包涵体见于中型神经元(向苍白球投射的GABA能神经元)和大型神经元(胆碱能中间神经元),前者在第III期开始出现,后者在第V期和第VI期开始出现。神经元和胶质包涵体也在第III期开始出现。神经元和神经胶质包涵体的数量和程度与PD分期有关(P<0.001)。这些发现提示在帕金森病进展过程中,固有的新纹状体神经元通过αS聚集而退化。
We immunohistochemically examined the neostriatum from 25 patients with symptomatic and presymptomatic Parkinson’s disease (PD) with various degrees of Lewy body pathology, using anti-phosphorylated α-synuclein (αS) antibody. These patients were classified according to the PD staging proposed by Braak et al. (Neurobiol Aging 24:197–211, 2003): stage II (αS pathology confined to the medulla oblongata and pontine tegmentum), stage III (αS pathology confined to the brainstem), stage IV (limbic stage), and stages V and VI (neocortical stage). αS immunohistochemistry revealed neuronal and glial cytoplasmic inclusions and neuritic changes in the neostriatum. αS inclusions were found in the medium-sized neurons (GABAergic neurons that project to the globus pallidus) and large neurons (cholinergic interneurons); the former began to appear at stage III and the latter was noted at stages V and VI. Neuritic changes and glial inclusions also began to appear at stage III. The numbers of neuronal and glial inclusions, and the extent of neuritic changes, correlated with the PD stage (P< 0.001). These findings suggest that intrinsic neostriatal neurons degenerate through αS aggregation during PD progression.