Mendonça D M F, Chimelli L, Martinez A M B
Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2005 Jun;38(6):925-33. doi: 10.1590/s0100-879x2005000600015. Epub 2005 Jun 1.
Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown etiology, affects motor neurons leading to atrophy of skeletal muscles, paralysis and death. There is evidence for the accumulation of neurofilaments (NF) in motor neurons of the spinal cord in ALS cases. NF are major structural elements of the neuronal cytoskeleton. They play an important role in cell architecture and differentiation and in the determination and maintenance of fiber caliber. They are composed of three different polypeptides: light (NF-L), medium (NF-M) and heavy (NF-H) subunits. In the present study, we performed a morphological and quantitative immunohistochemical analysis to evaluate the accumulation of NF and the presence of each subunit in control and ALS cases. Spinal cords from patients without neurological disease and from ALS patients were obtained at autopsy. In all ALS cases there was a marked loss of motor neurons, besides atrophic neurons and preserved neurons with cytoplasmic inclusions, and extensive gliosis. In control cases, the immunoreaction in the cytoplasm of neurons was weak for phosphorylated NF-H, strong for NF-M and weak for NF-L. In ALS cases, anterior horn neurons showed intense immunoreactivity in focal regions of neuronal perikarya for all subunits, although the difference in the integrated optical density was statistically significant only for NF-H. Furthermore, we also observed dilated axons (spheroids), which were immunopositive for NF-H but negative for NF-M and NF-L. In conclusion, we present qualitative and quantitative evidence of NF-H subunit accumulation in neuronal perikarya and spheroids, which suggests a possible role of this subunit in the pathogenesis of ALS.
肌萎缩侧索硬化症（ALS）是一种病因不明的神经退行性疾病，会影响运动神经元，导致骨骼肌萎缩、瘫痪和死亡。有证据表明，在ALS病例中，脊髓运动神经元中存在神经丝（NF）的积累。NF是神经元细胞骨架的主要结构成分。它们在细胞结构和分化以及纤维直径的确定和维持中发挥着重要作用。它们由三种不同的多肽组成：轻链（NF-L）、中链（NF-M）和重链（NF-H）亚基。在本研究中，我们进行了形态学和定量免疫组织化学分析，以评估对照病例和ALS病例中NF的积累情况以及各亚基的存在情况。在尸检时获取了无神经系统疾病患者和ALS患者的脊髓。在所有ALS病例中，除了萎缩的神经元和带有细胞质内含物的保留神经元外，运动神经元明显丧失，并且存在广泛的胶质增生。在对照病例中，神经元细胞质中磷酸化NF-H的免疫反应较弱，NF-M的免疫反应较强，NF-L的免疫反应较弱。在ALS病例中，前角神经元在神经元胞体的局部区域对所有亚基均显示出强烈的免疫反应性，尽管仅NF-H的积分光密度差异具有统计学意义。此外，我们还观察到扩张的轴突（球体），其对NF-H免疫阳性，但对NF-M和NF-L免疫阴性。总之，我们提供了NF-H亚基在神经元胞体和球体中积累的定性和定量证据，这表明该亚基在ALS发病机制中可能发挥作用。
