Sasaki S, Iwata M
Department of Neurology, Tokyo Women's Medical College, Japan.
Neurology. 1996 Aug;47(2):535-40. doi: 10.1212/wnl.47.2.535.
We studied the possible impairment of fast axonal transport in patients with amyotrophic lateral sclerosis (ALS) to gain some insight into the pathogenesis of the disease. We carried out an ultrastructural investigation of the proximal axons (axon hillock and initial segment) of the anterior horn neurons on samples from 11 ALS patients; specimens from 12 age-matched individuals who died of nonneurological diseases served as controls. Eighty-seven proximal axons that emanated directly from normal-appearing neurons were examined in each group of subjects. Increased smooth endoplasmic reticulum (SER) and the formation of bundles of fibrillary SER with a single unit membrane were not uncommonly observed in the initial segment of the patients with ALS. In some instances, there was loss of the parallel SER arrangement along the longitudinal axis. When viewed in transverse sections, the bundles had a tubular appearance. These morphologic changes of SER were exclusively demonstrated in patients with ALS. A marked increase or accumulation of mitochondria and lysosomes was more common in the proximal axons, particularly in the axon hillock, of ALS patients than of control subjects. The accumulation of these membrane-bounded cytoplasmic organelles suggests that fast axonal transport is impaired in the proximal axons of individuals with ALS. In addition, there were Lewy body-like hyaline inclusions, lipofuscin granules, and multiple membranous structures in the proximal axons. The presence of these unusual structures may also be a reflection of axonal transport dysfunction. By contrast, in the central chromatolytic neurons, there was not only a decrease in the number of neurofilaments in the axon hillock and initial segment, but also of mitochondria, lysosomes, and SER. In some instances, none of these cytoplasmic organelles was seen. These findings support the notion that the outflow of cytoplasmic constituents from the anterior horn cell body into the proximal axon may be impaired in central chromatolytic neurons.
我们研究了肌萎缩侧索硬化症（ALS）患者快速轴突运输可能存在的损害，以深入了解该疾病的发病机制。我们对11例ALS患者样本中的前角神经元近端轴突（轴丘和起始节段）进行了超微结构研究；选取12例死于非神经系统疾病的年龄匹配个体的标本作为对照。每组受试者中检查了87条直接发自外观正常神经元的近端轴突。在ALS患者的起始节段，常见滑面内质网（SER）增加以及形成具有单个单位膜的纤维状SER束。在某些情况下，沿纵轴的平行SER排列消失。横切面上，这些束呈管状外观。SER的这些形态学变化仅在ALS患者中出现。与对照组相比，ALS患者近端轴突，尤其是轴丘处，线粒体和溶酶体明显增多或聚集。这些膜结合的细胞质细胞器的聚集表明，ALS患者个体的近端轴突中快速轴突运输受损。此外，近端轴突中存在路易体样透明包涵体、脂褐素颗粒和多个膜性结构。这些异常结构的存在也可能反映了轴突运输功能障碍。相比之下，在中央染色质溶解的神经元中，不仅轴丘和起始节段的神经丝数量减少，线粒体、溶酶体和SER的数量也减少。在某些情况下，这些细胞质细胞器均未见到。这些发现支持了这样一种观点，即中央染色质溶解的神经元中，细胞质成分从前角细胞体向近端轴突的流出可能受损。
