Maturation process of TDP-43-positive neuronal cytoplasmic inclusions in amyotrophic lateral sclerosis with and without dementia
Maturation process of TDP-43-positive neuronal cytoplasmic inclusions in amyotrophic lateral sclerosis with and without dementia
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DOI：
10.1007/s00401-008-0396-9
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发表时间：
2008-08-01
影响因子：
12.7
通讯作者：
Wakabayashi, Koichi
中科院分区：
文献类型：
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作者：
Mori, Fumiaki;Tanji, Kunikazu;Wakabayashi, Koichi
为了阐明TDP-43阳性神经元包涵体的成熟过程，我们对10例肌萎缩侧索硬化症(ALS)患者和25例对照组的脑和脊髓多个区域进行了免疫组织化学和免疫电子显微镜观察。TDP-43免疫组织化学显示ALS中有3种类型的包涵体：丝蛋白样包涵体、圆形包涵体和点状包涵体。肌萎缩侧索硬化症患者均可见类蚕丝素包涵体。7例肌萎缩侧索硬化症患者前角有点状夹杂物，均为圆形，无圆形夹杂物。此外，仔细检查发现了两种类型的弥漫性点状胞浆染色：线状小束和点状颗粒。线状短波在所有ALS病例中都存在，但在25例对照中没有一例出现。相反，在所有ALS病例以及13例正常对照中的5例和12例患病对照中的7例中，均可检测到点状颗粒。免疫电子显微镜显示丝蛋白样包涵体由颗粒伴生的平行细丝组成。圆形和点状夹杂物由粒状丝状结构组成。然而，点状颗粒与线粒体相对应，不与泛素免疫染色，表明点状颗粒代表交叉反应。我们假设线束(“细丝”)聚集成更粗更长的线(“粗丝”)，而圆形夹杂物则由点状夹杂物产生。这些发现表明，尽管抗原性和超微结构相似，但丝蛋白样包涵体和圆形包裹体的形成过程存在差异。
To elucidate the maturation process of TDP-43-positive neuronal inclusions, we immunohistochemically and immunoelectron-microscopically examined multiple areas from the brain and spinal cord from ten patients with amyotrophic lateral sclerosis (ALS) and 25 control subjects. TDP-43 immunohistochemistry demonstrated three types of inclusions in ALS: skein-like, round, and dot-like inclusions. Skein-like inclusions were found in all cases of ALS. Dot-like inclusions were found in the anterior horn in seven cases of ALS, all of whom had round inclusions, but not in cases without round inclusions. In addition, careful examination revealed two types of diffuse punctate cytoplasmic staining: linear wisps and punctate granules. Linear wisps were present in all cases of ALS but in none of 25 controls. In contrast, punctate granules were detected in all cases of ALS as well as in five of 13 normal and in seven of 12 diseased controls. Immunoelectron-microscopy revealed that skein-like inclusions consisted of granule-associated parallel filaments. Round and dot-like inclusions were composed of granulo-filamentous structures. However, punctate granules corresponded to the mitochondria and were not immunostained with anti-ubiquitin, indicating that punctate granules represent cross-reaction. We assumed that linear wisps ("fine skein") aggregate as thicker and longer threads ("coarse skein"), whereas round inclusions arise from dot-like inclusions. These findings suggest that there are differences in the formation process between skein-like and round inclusions, despite the antigenic and ultrastructural similarities.