Length-dependent axo-terminal degeneration at the neuromuscular synapses of type II muscle in SOD1 mice.
Length-dependent axo-terminal degeneration at the neuromuscular synapses of type II muscle in SOD1 mice.
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DOI：
10.1016/j.neuroscience.2015.11.018
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发表时间：
2016-01-15
期刊：
影响因子：
3.3
通讯作者：
Farah MH
中科院分区：
文献类型：
--
作者：
Tallon C;Russell KA;Sakhalkar S;Andrapallayal N;Farah MH
在运动神经元疾病中，在任何临床症状开始出现之前存在延长的时间段。在此期间，远端轴突变性，或"死回"轴突病，在临床症状和运动神经元死亡发作之前开始发生。这种临床前变性是动物模型和人类患者中运动神经元疾病的标志。通常，在具有混合纤维类型的肌肉中，远端变性发生在支配IIb型肌纤维的快疲劳α运动轴突中，然后轴突支配缓慢的I型肌纤维。我们研究了在一个单纯的快速疲劳的α-运动轴突神经中的"死回"轴突病是否是一个长度依赖性过程。外侧胸神经（LTN）专门由运动神经支配的非常薄的皮肤最大肌（CMM），只包含II型神经肌肉突触。在肌萎缩侧索硬化症（ALS）的超氧化物歧化酶1（SOD1）突变小鼠模型中，我们从形态学和生理学两方面描述了LTN和CMM突触的特征。到60日龄时，尾部区域出现明显的“死背”现象，而吻部区域保持完整。支配尾部区域的较长轴突似乎更容易在SOD1小鼠中变性，这表明支配II型纤维的运动神经元的轴突变性是长度依赖性过程。此外，我们确定了LTN-CMM系统的简单性如何提供了一种更好的方法来研究ALS小鼠模型中的轴突变性，并可用于研究轴突保护和再生的可能治疗化合物。
In motor neuron diseases, there is a prolonged period of time before any clinical symptoms begin to appear. During this time, distal axonal degeneration, or “dying back” axonopathy, begins to occur before the onset of clinical symptoms and motor neuron death. This preclinical degeneration is a hallmark of motor neuron diseases in both animal models and human patients. Generally, in muscles with mixed fiber types, distal degeneration occurs in fast-fatigable α–motor axons innervating type IIb muscle fibers before axons innervating slow, type I muscle fibers. We investigated whether the “dying back” axonopathy in a pure fast-fatigable α–motor axon nerve is a length dependent process. The lateral thoracic nerve (LTN) exclusively consists of motor nerves that innervate the very thin cutaneous maximus muscle (CMM) that solely contains type II neuromuscular synapses. We characterized the LTN and CMM synapses both morphologically and physiologically in the superoxide dismutase 1 (SOD1) mutant mouse model of amyotrophic lateral sclerosis (ALS). By 60 days of age, there was a significant “dying back” phenomenon at the caudal region while the rostral region remained intact. The longer axons innervating the caudal region appear to be more susceptible to degeneration in the SOD1 mouse indicating that the axonal degeneration of motor neurons innervating type II fibers is a length dependent process. Additionally, we identified how the simplicity of the LTN-CMM system offers a better method to investigate axon degeneration in an ALS mouse model and may be used to investigate possible therapeutic compounds for axon protection and regeneration.