Motor Axonal Sprouting and Neuromuscular Junction Loss in an Animal Model of Charcot-Marie-Tooth Disease
Motor Axonal Sprouting and Neuromuscular Junction Loss in an Animal Model of Charcot-Marie-Tooth Disease
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DOI：
10.1097/nen.0b013e3181d1e60f
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发表时间：
2010-03-01
影响因子：
3.2
通讯作者：
Oliver, Sara Sancho
中科院分区：
文献类型：
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作者：
Ang, Eng-Tat;Schaefer, Ralf;Oliver, Sara Sancho
由外周髓鞘蛋白22（PMP 22）突变引起的腓骨肌萎缩症1A型（CMT 1A）的肌无力归因于导致去神经支配和肌肉萎缩的轴突病。涉及的潜在病理生理机制尚不清楚。我们研究了PMP 22转基因小鼠的运动性能、神经肌肉接头（NMJ）、生理参数和肌肉形态计量学。神经肌肉接头在PMP 22转基因小鼠后肢肌肉中逐渐丢失，但它们的运动性能在观察期间没有完全恶化。动物之间的缺陷存在相当大的变异性，包括偏侧性。横截面积和平均纤维大小的测量表明变量肌纤维萎缩后肢肌肉。有大量的伴随轴突发芽，神经肌肉接头的损失与轴突分支的累积长度呈负相关。在孤立的神经/肌肉制备突触传递研究表明变量部分肌肉去神经。乙酰胆碱的敏感性较高的突变体肌肉，和最大强直诱发的直接或间接刺激，具体的力量，湿重显着减少，在一些突变体肌肉。总之，在PMP 22转基因小鼠中存在部分肌肉去神经支配，并且轴突可能保留一些再生能力，但不能使肌肉重新神经支配。
Muscle weakness in Charcot-Marie-Tooth Type 1A disease (CMT1A) caused by mutations in peripheral myelin protein 22 (PMP22) has been attributed to an axonopathy that results in denervation and muscle atrophy. The underlying pathophysiological mechanisms involved are not understood. We investigated motor performance, neuromuscular junctions (NMJs), physiological parameters, and muscle morphometry of PMP22 transgenic mice. Neuromuscular junctions were progressively lost in hindlimb muscles of PMP22 transgenic mice, but their motor performance did not completely deteriorate during the observation period. There was considerable variability, including in laterality, in deficits among the animals. Cross-sectional areas and mean fiber size measurements indicated variable myofiber atrophy in hindlimb muscles. There was substantial concomitant axonal sprouting, and loss of neuromuscular junctions was inversely correlated with the accumulated length of axonal branches. Synaptic transmission studied in isolated nerve/muscle preparations indicated variable partial muscle denervation. Acetylcholine sensitivity was higher in the mutant muscles, and maximum tetanic force evoked by direct or indirect stimulation, specific force, and wet weights were markedly reduced in some mutant muscles. In summary, there is partial muscle denervation, and axons may retain some regenerative capacity but fail to reinnervate muscles in PMP22 transgenic mice.