The Golgi apparatus is fragmented in spinal cord motor neurons of amyotrophic lateral sclerosis with basophilic inclusions
The Golgi apparatus is fragmented in spinal cord motor neurons of amyotrophic lateral sclerosis with basophilic inclusions
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DOI：
10.1007/s004010100461
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发表时间：
2002-03-01
影响因子：
12.7
通讯作者：
Gonatas, NK
中科院分区：
文献类型：
--
作者：
Fujita, Y;Okamoto, K;Gonatas, NK
肌萎缩侧索硬化症（ALS）中神经元死亡的机制尚不清楚。细胞质成分以各种包涵体形式的病理性聚集可能在神经元死亡的发病机制中起作用。运动神经元胞浆内嗜碱性包涵体（BI）常见于散发性幼年型ALS。这些夹杂物的功能意义尚不清楚，即，它们是否代表从细胞质中分离异常产物的保护性反应，或不可逆神经元损伤的迹象。为了深入了解BI的意义，我们询问了BI神经元是否具有完整或片段化的高尔基体（GA），这是一种神经元变性的迹象，不仅在散发性和家族性ALS中报告了Cu/Zn超氧化物歧化酶基因（SOD 1）突变，而且在表达SOD 1 G93 A突变的转基因小鼠中也有报道。在这些小鼠脊髓运动神经元GA的碎片被发现瘫痪发作前几个月。我们在这里报告说，所有的神经元轴承的夹杂物表现出碎片和GA的数量减少。这些结果表明，共同的发病机制参与生产的BI和GA的碎片。
The mechanisms of neuronal death in amyotrophic lateral sclerosis (ALS) are not known. A pathological aggregation of cytoplasmic constituents in the form of variety of inclusions may play a role in the pathogenesis of neuronal death. Cytoplasmic basophilic inclusions (BIs) in motor neurons are commonly found in sporadic juvenile ALS. The functional significance of these inclusions is not known, i.e., whether they represent a protective reaction for the isolation of abnormal products from the cytoplasm, or a sign of irreversible neuronal damage. To gain insights on the significance of BIs we asked whether neurons with BIs had an intact or fragmented Golgi apparatus (GA), a sign of neuronal degeneration reported not only in sporadic and familial ALS with mutations of the Cu/Zn superoxide dismutase gene (SOD1), but also in transgenic mice expressing the G93A mutation of SOD1. In these mice fragmentation of the GA of spinal cord motor neurons was found months before the onset of paralysis. We report here that all neurons bearing the inclusions showed fragmentation and reduced number of GA. These results suggest that common pathogenetic mechanisms are involved in the production of BIs and in the fragmentation of the GA.