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

本文对10例正常人腰髓的大前角细胞轴突近端进行了观察。光镜下，正常神经元轴索丘加起始段(AH+IS)的长度为64.0±12.3 mm(平均+扫描电子显微镜)，最薄的部分直径为2.40±0.30 mm(平均+扫描电子显微镜)，范围为1.3 2~3.92 mm。在电子显微镜下，初始段的细胞膜由一层电子致密物质(底膜)组成。起始节的细胞质内含有许多神经丝，与起始节的纵轴平行。在神经丝中可见溶酶体、光滑内质网、致密小体和泡状轮廓以及线粒体。在髓鞘之初，轴浆含有线粒体、许多神经细丝和偶尔的溶酶体。我们还测量了直径…3例肌萎缩侧索硬化症(ALS)患者、1例下运动神经元病(LMND)患者和11例对照组腰髓轴突起始部最远端、前角细胞大小和AH+长度均显著增加。对甲苯胺蓝染色的连续塑料切片和电子显微镜进行了研究。共观察到214个轴突直接来自躯体(n=207)和初级树突(n=7)。近端有髓轴突(ALS组155个轴突中有24个轴突，LMND组59个轴突中有17个轴突)在第一个节间肿胀，大部分肿胀延伸到起始节段的中部。电子显微镜显示，与其体节直接相连的近端轴突(起始节和第一节间)的肿胀主要由10 nm长的神经丝堆积组成。肌萎缩侧索硬化症(ALS)组(n=15 5)最远端起始段的平均直径(p&lt；0.0001)明显大于对照组(n=2 5 8)(p&lt；0.0001)。此外，肌萎缩侧索硬化症患者非肿胀轴突起始段的最远端平均直径也大于对照组(p&lt；0.0001)。核周和轴突丘与外观正常且肿胀的近端轴突相连，其树突几乎总是显示正常。这些结果表明，反映神经细丝异常堆积的轴突起始段直径的增加代表了运动神经元病的早期病理变化，在疾病过程的早期，这部分轴突的缓慢轴突运输可能受到损害。ALS(P&lt；0.0001)和LMND(P&lt；0.0001)中发出轴突的正常细胞体的平均大小小于对照组。在具有正常外观的起始较少的ALS之间，AH+IS长度没有显著差异

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