Study of the proximal axon of anterior horn neurons in amyotrophic lateral sclerosis

本文对10例正常人尸体解剖腰索的大前角细胞轴突近端部分进行了研究。光镜下，正常神经元（n=77）轴突小丘加初始节段（AH+IS）长度为64.0 + 12.3 mm（平均+ SEM），范围为47.5 ~ 110.0 mm，初始节段最薄部分直径为2.40 + 0.30 mm（平均+ SEM），范围为1.32 ~ 3.92 mm。在电子显微镜下，初始段的细胞膜由一层电子致密材料（下涂层）组成。初始节段的细胞质包含许多神经丝，平行于初始节段的纵轴。在神经丝中可见溶酶体、光滑内质网、致密体和囊泡轮廓以及线粒体。髓鞘起始处，轴质含有线粒体、许多神经丝和偶有溶酶体。我们还测量了3例肌萎缩性侧索硬化症（ALS）患者、1例下肢运动神经元疾病（LMND）患者和11例对照患者的轴突起始段最远端部分的直径…More r、前角细胞的神经元大小和腰髓AH+IS的长度。研究了甲苯胺蓝染色的连续塑料切片和电子显微镜。共观察到214个轴突直接发源于躯体（n=207）和初级树突（n=7）。大约19%的近端有髓轴突（ALS患者155个轴突中有24个，LMND患者59个轴突中有17个）在第一节间肿胀，大部分肿胀延伸到初始节段的中部。电镜观察显示，与体体直接相连的近端轴突（初始节段和第一节间）肿胀主要由10 nm的神经丝堆积组成。ALS患者（n=155）和LMND患者（n= 5.9）的最远端初始节段平均直径明显大于对照组（n=258）。此外，ALS患者未肿胀的轴突最远端部分的平均直径比对照组大（n=131）（p<0.0001）。与正常的近端轴突相连的核周丘和轴突丘及其树突几乎总是正常的。这些发现表明，反映神经丝异常积聚的轴突初始段直径增加代表了运动神经元疾病的早期病理改变，并且在疾病过程的早期阶段，神经丝的缓慢轴突运输可能在轴突的这一部分受损。与对照组相比，ALS（p<0.0001）和LMND（p<0.0001）的轴突发出的正常细胞体的平均大小更小。出现正常起首字母较少的ALS患者AH+IS长度差异无统计学意义

The proximal portions of axons of large anterior horn cells were investigated in the lumbar cords of 1 0 normal human autopsy cases. Light-microscopically, the length of the axon hillock plus initial segment (AH+IS) of normal-looking neurons (n=77) was 64.0 + 12.3 mm (average + SEM), ranging from 47.5 to 110.0 mm, while the diameter of the thinnest portion of the initial segment was 2.40 + 0.30 mm (average + SEM), ranging from 1.32 to 3.92 mm. Electron-microscopically, the cell membrane of the initial segment consisted of a layer of electron-dense material (undercoating). The cytoplasm of the initial segment contained many neurofilaments, running parallel to the longitudinal axis of the initial segment. Among the neurofilaments, lysosomes, smooth endoplasmic reticulum, dense bodies and vesicular profiles aswell as mitochondria were seen. At the beginning of the myelin sheath, the axoplasm contained mitochondria, many neurofilaments and occasional lysosomes. We also measured the diamete … More r of the most distal portion of the axonal initial segment, the neuronal size of anterior horn cells, and the length of AH+IS in the lumbar spinal cord in three patients with amyotrophic lateral sclerosis (ALS), one with lower motor neuron disease (LMND) and 11 controls. Serial plastic sections stained with toluidine blue and electron micrographs were studied. A total of 214 axons directly emanating from the somata (n=207) and the primary dendrites (n=7) were observed in the patients. Approximately 19% of the proximal myelinated axons (24 axons out of 155 in ALS, and 17 axons out of 59 in LMND) were swollen at the first internode, and most of the swellings extended to the middle portion of the initial segment. Electron microscopy showed that the swellings of the proximal axons (the initial segment and the first internode) directly connected with their somata consisted mainly of accumulations of 10-nm neurofilaments. The average diameter of the most distal initial segment was markedly larger in ALS(n=155)(p<0.0001) and LMND(n=5 9)(p<0.0001) than in the controls (n=258). Moreover, the average diameter of the most distal portion of even normal-appearing initial segments of the non-swollen axons was larger in ALS(n=131)(p<0.0001) than in the controls. The perikarya and axon hillocks connected with the normal-appearing and swollen proximal axons and their dendrites almost always appeared normal. These findings suggest that increasing diameter of the axonal initial segment which reflects the abnormal accumulation of neurofilaments represents an early pathological change in motor neuron disease and that slow axonal transport of neurofilaments is probably impaired in this portion of the axon at an early stage in the disease process. The average size of the normal-appearing cell bodies from which axons emanated was smaller in ALS(p<0.0001) and LMND(p<0.0001) than in the controls. There was no significant difference in the AH+IS length among ALS having normal-appearing initia Less