Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis-causing mutations.
Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis-causing mutations.
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DOI：
10.1002/cne.23848
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Valdez G
中科院分区：
文献类型：
--
作者：
Vaughan SK;Kemp Z;Hatzipetros T;Vieira F;Valdez G
肌萎缩性侧索硬化症（ALS）是一种主要针对运动系统的神经退行性疾病。尽管人们对ALS对运动神经元和神经胶质细胞的影响了解甚多，但对其对本体感觉神经元的影响知之甚少。本研究在SOD1G93A和TDP43A315T转基因小鼠中检测了ALS相关突变小鼠的本体感觉神经元。在这两种转基因系中，我们发现在向胫骨前肌注射这种逆行示踪剂5天后，它们的体细胞中含有荧光标记霍乱毒素的本体感觉神经元减少了。我们询问这是否由于神经元丢失或周围神经末梢的选择性变性。我们发现SOD1G93A症状小鼠与对照小鼠本体感觉神经元体细胞的总数和大小没有差异。然而，对肌肉本体感觉神经末梢的分析显示，在疾病症状期之前，肌肉纺锤体的Ia/II本体感觉神经末梢发生了早期和显著的改变。虽然SOD1G93A小鼠的α-运动轴突发生了这些变化，但TDP43A315T转基因小鼠的Ia/II感觉神经末梢在α-运动轴突无明显变化的情况下发生了退化。接下来，我们询问脊髓的本体感觉神经末梢是否同样受到影响，并发现在症状期和周围神经末梢开始退化后，终止于α-运动神经元的神经末梢受到影响。总的来说，我们发现Ia/II本体感觉神经元受到als引起的突变的影响，病理改变始于它们的周围神经末梢。
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1G93A and TDP43A315T transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1G93A and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at α-motor axons in SOD1G93A mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in α-motor axons in TDP43A315T transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on α-motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS-causing mutations, with pathological changes starting at their peripheral nerve endings.
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