Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man
Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man
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DOI：
10.1016/j.expneurol.2003.10.004
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发表时间：
2004-02-01
影响因子：
5.3
通讯作者：
Glass, JD
中科院分区：
文献类型：
--
作者：
Fischer, LR;Culver, DG;Glass, JD
SOD I突变小鼠是最广泛使用的人类肌萎缩侧索硬化（ALS）模型。为了确定运动神经元疾病的病理变化在何处以及何时开始，我们对SODIG 93 A小鼠的疾病进展进行了全面的时空分析。在多个年龄的相同小鼠中，在神经肌肉接头（NMJ）、前根和脊髓处进行定量病理学分析。此外，尸检时检查了一例意外死亡的散发性ALS患者。小鼠在80天时变得临床虚弱，并在131 +/-5天时死亡。在第47天，40%的终板失神经支配，而没有证据表明前根或细胞体损失。在第80天，60%的前根轴突丢失，但没有运动神经元的损失。运动神经元的损失在100天内进行得很好。运动神经元周围的小胶质细胞和星形胶质细胞的激活直到远端轴突变性发作后才被发现。ALS患者的尸检显示肌肉的去神经支配和神经再支配变化，但运动神经元表现正常。我们的结论是，在这个广泛研究的人类ALS动物模型中，在这个单一的人类病例中，运动神经元病理学始于远端轴突，并以“死回”模式进行。(C)2003年爱思唯尔公司All rights reserved.
The SOD I mutant mouse is the most widely used model of human amyotrophic lateral sclerosis (ALS). To determine where and when the pathological changes of motor neuron disease begins, we performed a comprehensive spatiotemporal analysis of disease progression in SODIG93A Mice. Quantitative pathological analysis was performed in the same mice at multiple ages at neuromuscular junctions (NMJ), ventral roots, and spinal cord. In addition, a patient with sporadic ALS who died unexpectedly was examined at autopsy. Mice became clinically weak at 80 days and died at 131 +/- 5 days. At 47 days, 40% of end-plates were denervated whereas there was no evidence of ventral root or cell body loss. At 80 days, 60% of ventral root axons were lost but there was no loss of motor neurons. Motor neuron loss was well underway by 100 days. Microglial and astrocytic activation around motor neurons was not identified until after the onset of distal axon degeneration. Autopsy of the ALS patient demonstrated denervation and reinnervation changes in muscle but normal appearing motor neurons. We conclude that in this widely studied animal model of human ALS, and in this single human case, motor neuron pathology begins at the distal axon and proceeds in a "dying back" pattern. (C) 2003 Elsevier Inc. All rights reserved.