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

肌萎缩侧索硬化症前角神经元近端轴突的研究

• 批准号: 01570458
• 负责人: SASAKI Shoichi
• 金额: $ 1.34万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570458/
• 关键词: Amyotrophic lateral sclerosis; Motor neuron disease; Anterior horn neuron; Proximal axon; Axonalinitial Segment; Axonal transport; Neurofilament; Ultrastructure; 筋妥縮性側索硬化症; initial segment; proximal axon; ultrastructure; amyotrophic lateral sc

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

在 1 0 例正常人体尸检病例的腰索中研究了大前角细胞轴突的近端部分。光镜下，正常神经元（n = 77）的轴突小丘加上初始段（AH + IS）的长度为64.0 + 12.3 mm（平均值+ SEM），范围为47.5至110.0 mm，而初始段最细部分的直径为2.40 + 0.30 mm（平均值+ SEM），范围为1.32至1.32 mm。 3.92 毫米。在电子显微镜下，初始部分的细胞膜由一层电子致密材料（底涂层）组成。初始节段的细胞质含有许多神经丝，平行于初始节段的纵轴。在神经丝中，可以看到溶酶体、光滑内质网、致密体和囊泡轮廓以及线粒体。在髓鞘的起始部分，轴浆含有线粒体、许多神经丝和偶尔的溶酶体。我们还测量了 3 名肌萎缩侧索硬化症 (ALS) 患者、1 名下运动神经元疾病 (LMND) 患者和 11 名对照患者的轴突起始段最远端部分的直径、前角细胞的神经元大小以及腰脊髓 AH+IS 的长度。研究了用甲苯胺蓝染色的系列塑料切片和电子显微照片。在患者中观察到总共 214 个直接源自体细胞 (n=207) 和初级树突 (n=7) 的轴突。大约 19% 的近端有髓轴突（ALS 中 155 个轴突中的 24 个，LMND 中 59 个轴突中的 17 个）在第一节间肿胀，并且大多数肿胀延伸到初始节段的中间部分。电镜显示，与其体细胞直接相连的近端轴突（起始节段和第一节间）的肿胀主要由10纳米神经丝的堆积组成。 ALS(n=155)(p<0.0001)和LMND(n=5·9)(p<0.0001)中最远端初始节段的平均直径明显大于对照组(n=258)。此外，ALS 组（n=131）（p<0.0001）中非肿胀轴突的甚至外观正常的初始段的最远端部分的平均直径也比对照组大。与正常外观和肿胀的近端轴突相连的核周和轴突小丘及其树突几乎总是显得正常。这些发现表明，反映神经丝异常积累的轴突起始段直径的增加代表了运动神经元疾病的早期病理变化，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中受损。 ALS (p<0.0001) 和 LMND (p<0.0001) 中发出轴突的正常细胞体的平均尺寸小于对照组。初始表现正常的 ALS 中 AH+IS 长度无显着差异 较少

项目成果

SHOICHI SASAKI: "Proceedings of the 1st Workshop on Neuron pathology of Retrovirus Infections" Iwasaki Y, 131 (1989)

SHOICHI SASAKI：“第一届逆转录病毒感染神经元病理学研讨会论文集”Iwasaki Y，131 (1989)

佐々木彰一: "Bunina小体およびBunina様小体の分析電顕による検討" 神経内科. 25. 262-267 (1986)

Shoichi Sasaki：“通过分析电子显微镜研究布尼纳小体和布尼纳样小体”神经病学 25. 262-267 (1986)。

SHOICHI SASAKI: "Immunocytochemical and ultrastructural studies of hyaline inclasions in sporadic motor neuron disease" Acta Neuropathologica. 82. 295-301 (1991)

SHOICHI SASAKI：“散发性运动神经元疾病中透明浸润的免疫细胞化学和超微结构研究”《神经病理学报》。

SHOICHI SASAKI: "Observation of proxinal protions of axons of anterior horn cells in the human spinal cord" Acta Anatomica. 139. 26-30 (1990)

SHOICHI SASAKI：“人类脊髓前角细胞轴突近端部分的观察”《解剖学报》。

SHOICHI SASAKI: "Observation of proximal portions of axons of anterior horn cells in the human spinal corol" Acta Anatomica. 139. 26-30 (1990)

SHOICHI SASAKI：“人类脊髓前角细胞轴突近端部分的观察”《解剖学报》。