Gale A N, Gomez S, Duchen L W
Brain. 1982 Jun;105(Pt 2):373-93. doi: 10.1093/brain/105.2.373.
The peripheral nerves of the Trembler mouse are hypomyelinated. The effects of the neuropathy on muscle and motor end-plate morphology, and on neuromuscular transmission in slow-twitch (soleus) and fast-twitch (extensor digitorum longus) muscle are reported. After forming normally, motor end-plates developed ultraterminal sprouts by about 18 days of age in deep, slow-twitch muscles. The only ultrastructural abnormality in muscle at this age was disruption of Z-lines. Ultraterminal sprouting progressed, and by about 3 months the innervation zone consisted of a mass of branching axons associated in places with cholinesterase activity. The ultrastructure of end-plates became abnormal. Fascicular atrophy was present in older Tremblers and the ultrastructural morphology of muscle fibres became disorganized with accumulation of subsarcolemmal granular material. Abnormal muscle fibres were innervated by axonal sprouts. The superficial, predominantly fast-twitch, muscles showed milder changes at all ages even though the nerves supplying them were hypomyelinated. Studies of neuromuscular transmission showed that soleus retained its slow-twitch and extensor digitorum longus its fast-twitch characteristics, and miniature end-plate potentials were of normal frequency and amplitude. The latency of end-plate potentials and the refractory period of transmission were prolonged in both soleus and extensor digitorum longus. With repetitive stimulation at 50 Hz a cyclical pattern of responses and failures occurred which was probably caused by intermittent conduction block along the peripheral nerve. Although the pathological changes in Trembler muscle were like those of partial denervation, atrophic muscles contained an abundance of axons and there was no evidence of axonal degeneration. The changes in muscle are therefore a consequence of hypomyelination without axonal loss. Since slow-twitch muscles are normally subjected to prolonged stimulation, failure of Trembler axons to conduct sustained trains of stimuli in vivo may contribute to the development of pathological changes in slow-twitch muscle. Hypomyelimated axons may be capable of conducting short bursts of impulses, however, which is the pattern of stimulation in fast-twitch muscle in vivo, so that fast-twitch muscle fibres and end-plates remain relatively spared.
颤抖小鼠的外周神经髓鞘形成不全。本文报道了该神经病变对肌肉和运动终板形态以及对慢肌（比目鱼肌）和快肌（趾长伸肌）神经肌肉传递的影响。运动终板在正常形成后，在深部慢肌中约18日龄时会发育出超终末芽。这个年龄段肌肉中唯一的超微结构异常是Z线的破坏。超终末芽继续发育，到约3个月时，神经支配区由一团分支轴突组成，这些轴突在某些部位与胆碱酯酶活性相关。终板的超微结构变得异常。年龄较大的颤抖小鼠出现束状萎缩，肌纤维的超微结构形态变得紊乱，肌膜下颗粒物质积聚。异常肌纤维由轴突芽支配。浅表的、主要为快肌的肌肉在所有年龄段的变化都较轻，尽管支配它们的神经髓鞘形成不全。神经肌肉传递研究表明，比目鱼肌保留了其慢肌特性，趾长伸肌保留了其快肌特性，微小终板电位的频率和幅度正常。比目鱼肌和趾长伸肌的终板电位潜伏期和传递不应期均延长。以50Hz重复刺激时，会出现反应和衰竭的周期性模式，这可能是由外周神经的间歇性传导阻滞引起的。尽管颤抖小鼠肌肉的病理变化类似于部分去神经支配，但萎缩肌肉中含有大量轴突，且没有轴突退变的证据。因此，肌肉的变化是髓鞘形成不全而非轴突丧失的结果。由于慢肌通常受到长时间刺激，颤抖小鼠轴突在体内无法传导持续的刺激序列可能导致慢肌病理变化的发展。然而，髓鞘形成不全的轴突可能能够传导短串冲动，这是体内快肌的刺激模式，因此快肌纤维和终板相对幸免。
