Velasco Elena, Gledhill Teresa, Linares Cristhian, Roschman-González Antonio
Laboratorio de Microscopía Electrónica, Escuela de Medicina José María Vargas, Facultad de Medicina, Universidad Central de Venezuela.
Invest Clin. 2008 Dec;49(4):469-86.
We studied the short and long term ultrastructural changes produced by botulinum neurotoxin type A injected in vivo, at a sublethal dose, in mouse levator auris longus muscle. The neurotoxin had a temporary effect on nerve terminals which consisted in a generalized paralysis, that affected the following features of the neuromuscular sample's morphology: size of the nerve terminals, vesicle population, mitochondrial appearance, Schwann cell's morphology, development and distribution of post-synaptic membrane folds, and nuclear morphology of the different elements of the motor end plate. Besides, the amount of endomysial connective tissue was significantly greater compared to non-intoxicated cases, and these changes were more notorious during the first couple of weeks. 20 to 25 days after the injection, during the recovery phase, we observed nerve terminals with a variable appearance: some completely degenerated, enveloped by Schwann cell processes, and new contacts characterized ultrastructurally for their small size, scarce vesicles, partially enveloped by Schwann cells, early myelinized axons and barely developed synaptic folds. Sixty days after the injection, the axon terminal recovered its normal appearance: synaptic vesicles filled the axon's cytoplasm, and the mitochondria showed normal appearing cristae and electronic densities. We conclude that botulinum neurotoxin type A produces changes related to denervation of the nerve terminals and affects the motor end plate components. Schwann cells play an important role both in the morphofuntional recovery of nerve terminals and in their degradation.
我们研究了以亚致死剂量在体内向小鼠耳长肌注射A型肉毒杆菌神经毒素所产生的短期和长期超微结构变化。该神经毒素对神经末梢有暂时影响,表现为全身性麻痹,影响神经肌肉样本形态的以下特征:神经末梢大小、囊泡数量、线粒体外观、施万细胞形态、突触后膜褶皱的发育和分布以及运动终板不同成分的核形态。此外,与未中毒的情况相比,肌内膜结缔组织的量显著增加,并且这些变化在最初几周更为明显。注射后20至25天,在恢复阶段,我们观察到神经末梢外观各异:一些完全退化,被施万细胞突起包裹,新的接触点在超微结构上的特征是体积小、囊泡稀少、部分被施万细胞包裹、轴突早期髓鞘化且突触褶皱发育不良。注射后60天,轴突末梢恢复正常外观:突触囊泡充满轴突细胞质,线粒体显示出正常的嵴和电子密度。我们得出结论,A型肉毒杆菌神经毒素会产生与神经末梢去神经支配相关的变化,并影响运动终板成分。施万细胞在神经末梢的形态功能恢复及其降解过程中都发挥着重要作用。