Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan.
Neuropathol Appl Neurobiol. 2012 Oct;38(6):559-71. doi: 10.1111/j.1365-2990.2011.01229.x.
Multiple system atrophy (MSA) is pathologically characterized by the formation of α-synuclein-containing glial cytoplasmic inclusions (GCIs) in oligodendrocytes. However, the mechanisms of GCI formation are not fully understood. Cellular machinery for the formation of aggresomes has been linked to the biogenesis of the Lewy body, a characteristic α-synuclein-containing inclusion of Parkinson's disease and dementia with Lewy bodies. Here, we examined whether GCIs contain the components of aggresomes by immunohistochemistry.
Sections from five patients with MSA were stained immunohistochemically with antibodies against aggresome-related proteins and analysed in comparison with sections from five patients with no neurological disease. We evaluated the presence or absence of aggresome-related proteins in GCIs by double immunofluorescence and immunoelectron microscopy.
GCIs were clearly immunolabelled with antibodies against aggresome-related proteins, such as γ-tubulin, histone deacetylase 6 (HDAC6) and 20S proteasome subunits. Neuronal cytoplasmic inclusions (NCIs) were also immunopositive for these aggresome-related proteins. Double immunofluorescence staining and quantitative analysis demonstrated that the majority of GCIs contained these proteins, as well as other aggresome-related proteins, such as Hsp70, Hsp90 and 62-kDa protein/sequestosome 1 (p62/SQSTM1). Immunoelectron microscopy demonstrated immunoreactivities for γ-tubulin and HDAC6 along the fibrils comprising GCIs.
Our results indicate that GCIs, and probably NCIs, share at least some characteristics with aggresomes in terms of their protein components. Therefore, GCIs and NCIs may be another manifestation of aggresome-related inclusion bodies observed in neurodegenerative diseases.
多系统萎缩（MSA）在病理学上的特征是少突胶质细胞中形成含有α-突触核蛋白的神经胶质细胞质包涵体（GCIs）。然而，GCIs 形成的机制尚不完全清楚。形成聚集物的细胞机制与路易体的生物发生有关，路易体是帕金森病和路易体痴呆症中特征性的含有α-突触核蛋白的包涵体。在这里，我们通过免疫组织化学检查了 GCIs 是否含有聚集物的成分。
用针对聚集物相关蛋白的抗体对来自 5 例 MSA 患者的切片进行免疫组织化学染色，并与来自 5 例无神经疾病患者的切片进行比较。我们通过双重免疫荧光和免疫电镜评估 GCIs 中聚集物相关蛋白的存在情况。
GCIs 与聚集物相关蛋白如γ-微管蛋白、组蛋白去乙酰化酶 6（HDAC6）和 20S 蛋白酶体亚单位的抗体清楚地免疫标记。神经元细胞质包涵体（NCIs）也对这些聚集物相关蛋白呈免疫阳性。双重免疫荧光染色和定量分析表明，大多数 GCIs 含有这些蛋白以及其他聚集物相关蛋白，如热休克蛋白 70（Hsp70）、热休克蛋白 90（Hsp90）和 62kDa 蛋白/自噬相关蛋白 1（p62/SQSTM1）。免疫电镜显示 GCIs 纤维中存在γ-微管蛋白和 HDAC6 的免疫反应性。
我们的结果表明，GCIs，可能还有 NCIs，在蛋白成分方面与聚集物至少具有一些共同特征。因此，GCIs 和 NCIs 可能是神经退行性疾病中观察到的聚集物相关包涵体的另一种表现形式。
