CHANGES IN MOTOR INNERVATION AND CHOLINESTERASE LOCALIZATION INDUCED BY BOTULINUM TOXIN IN SKELETAL MUSCLE OF MOUSE - DIFFERENCES BETWEEN FAST AND SLOW MUSCLES
CHANGES IN MOTOR INNERVATION AND CHOLINESTERASE LOCALIZATION INDUCED BY BOTULINUM TOXIN IN SKELETAL MUSCLE OF MOUSE - DIFFERENCES BETWEEN FAST AND SLOW MUSCLES
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DOI：
10.1136/jnnp.33.1.40
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发表时间：
1970-01-01
影响因子：
11
通讯作者：
DUCHEN, LW
中科院分区：
文献类型：
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作者：
DUCHEN, LW
结果 临床结果 注射毒素后约 24 小时内出现右后腿肌肉麻痹。还存在短暂的全身毒性症状，包括肌肉无力和呼吸困难以及肋骨后退。右腿明显瘫痪三四个星期，四肢肌肉萎缩明显。在注射毒素后的最初几周内，小鼠无法跖屈足部，从而无法在攀爬活动中抓住笼子的栏杆。足部使用的恢复和跖屈的重新出现大约在第五周开始，到第十周时，小鼠可以很好地使用腿和足部，尽管不正常。即使是存活时间最长的动物在攀爬活动中也倾向于不使用右后腿和右脚，有时右脚会被笨拙地使用或失去抓地力，这在正常小鼠中是最不寻常的发现。 组织学在正常小鼠中，梭外骨骼肌的神经支配符合哺乳动物中观察到的一般神经支配模式（Coers 和 Woolf，1959）。神经干在神经血管门进入肌肉，当神经干和神经束穿过肌肉时，会发生许多轴突分支。在肌肉中部附近，每个神经束分裂成一束单髓鞘轴突，每个轴突在终止于单个梭外肌纤维的运动终板之前前进一小段距离。末端树枝化的脆弱的无髓鞘神经纤维位于肌膜膜的沟槽中，与肌膜膜内折叠形成的“神经下装置”紧密相连（Couteaux，1958），其中胆碱酯酶活性特别集中。神经下器的形状和大小随截面的平面而变化。当整个终板包含在剖面中时，神经下装置的外观通常是具有内部分支的环状结构，特别是在腓肠肌中（图1）。通常看不到从外围向外伸出的树枝。在pH 56 下在碘化乙酰硫胆碱底物中孵育显示出比在pH 5 2 下更多的反应产物。在iso-OMPA 存在下，神经下装置中的反应强度略有降低。在丁酰硫代胆碱底物中孵育显示非特异性胆碱酯酶活性，该活性被 iso-OMPA 抑制。当孵育时间限制在 10 至 15 分钟时，在有髓神经纤维本身中看不到反应产物，但在 pH 5 6 孵育 30 分钟或更长时间时可以看到反应产物。与本研究结果相关的小鼠梭外肌纤维正常神经支配的要点是（1）每条肌纤维均由单个前末端有髓轴突支配，该轴突在离开神经束后通常不分支；（2）每条运动神经纤维终止于运动终板内，也就是说，除了与具有胆碱酯酶活性的神经下装置密切相关外，没有运动神经纤维终止于其他地方；（3）没有运动神经纤维
RESULTSCLINICAL Paralysis of the muscles of the right hind legdeveloped within about24 hours after the injection of the toxin. There were also transient signs of generalized toxicity which consisted of muscular weakness and respiratory difficulty with costal recession. The right leg was obviously paralysed for three to four weeks and atrophy of the limb muscles became apparent. During the first few weeks after the injection of toxin, the mouse was unable to plantarflex the foot, which could not be used for gripping the bars of the cage during climbing activity. Recovery of the use of thefoot and the reappearance of plantar flexion began at about the fifth week and by the tenth week the mouse could use the leg and foot well, though not normally. Even the longest surviving animals tended not to use the right hind leg and foot during climbing activity and sometimes the right foot would be used clumsily or miss its grip, a most unusual finding ina normal mouse.HISTOLOGICAL In the normal mouse the innervation of extrafusal skeletal muscle conforms to the general pattern of innervation seen in mammals (Coers and Woolf, 1959). Nerve trunks enter the muscle at the neurovascular hilum and much axonal branching takes place in the nerve trunks and bundles as they spread through the muscle. Near the middle of the muscle each nerve bundle breaks up into a spray of singl_ myelinated axons each of which proceeds for a short distance before terminating in the motor end-plate of a single extrafusal muscle fibre. The delicate unmyelinated nerve fibres of the terminal arborization lie in gutters of the sarcolemmal membrane in close apposition to the'subneural apparatus' formed by infoldings of the sarcolemmal membrane (Couteaux, 1958) in which cholinesterase activity is particularly concentrated. The shape and size of the subneural apparatus varies with the plane of the section. When the whole end-plate is included in the section the appearance of the subneural apparatus is often, particularly in gastrocnemius, that of a ring-like structure with internal branches (Fig. 1). Branches are not usually seen pointing outwards from the periphery. Incubation in acetylthiocholine iodide substrate at pH 56 demonstrates more reaction product than at pH 5 2. In the presence of iso-OMPA theintensity of the reaction in subneural apparatuses is slightly reduced. Incubation in butyrylthiocholine substrate shows nonspecific cholin-esterase activity which is inhibited by iso-OMPA. When the incubation is restricted to 10 to 15 minutes no reaction product is seen in the myelinated nerve fibres themselves, but this is seen at pH 5 6 incubated for 30 minutes or more. The important points about the normal in-nervation of extrafusal muscle fibres in the mouse relevant to the findings in this work are (1) each muscle fibre is innervated by a single preterminal myelinated axon which usually does not branch after leaving the nerve bundle;(2) each motor nerve fibre terminates within a motor end-plate-that is, there are no motor nerve fibres which end elsewhere than in close relationship to a subneural apparatus with its cholinesterase activity;(3) no motor