Mori Fumiaki, Tanji Kunikazu, Zhang Hai-Xin, Nishihira Yasushi, Tan Chun-Feng, Takahashi Hitoshi, Wakabayashi Koichi
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
Acta Neuropathol. 2008 Aug;116(2):193-203. doi: 10.1007/s00401-008-0396-9. Epub 2008 Jun 17.
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.
为阐明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）患者及25名对照者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检查。TDP-43免疫组织化学显示ALS中有三种类型的包涵体：绞丝状、圆形和点状包涵体。绞丝状包涵体在所有ALS病例中均有发现。点状包涵体在7例ALS患者的前角中发现，这些患者均有圆形包涵体，而在无圆形包涵体的病例中未发现。此外，仔细检查发现两种弥漫性点状细胞质染色：线性细丝和点状颗粒。线性细丝存在于所有ALS病例中，但在25名对照者中均未发现。相比之下，点状颗粒在所有ALS病例以及13名正常对照者中的5例和12名疾病对照者中的7例中均有检测到。免疫电子显微镜显示绞丝状包涵体由颗粒相关的平行细丝组成。圆形和点状包涵体由颗粒丝状结构组成。然而，点状颗粒对应于线粒体，未被抗泛素免疫染色，表明点状颗粒代表交叉反应。我们推测线性细丝（“细绞丝”）聚集成更粗更长的细丝（“粗绞丝”），而圆形包涵体由点状包涵体产生。这些发现表明，尽管绞丝状和圆形包涵体在抗原性和超微结构上有相似之处，但它们在形成过程中存在差异。
