Functional repair of motor endplates after botulinum neurotoxin type A poisoning:: Biphasic switch of synaptic activity between nerve sprouts and their parent terminals
Functional repair of motor endplates after botulinum neurotoxin type A poisoning:: Biphasic switch of synaptic activity between nerve sprouts and their parent terminals
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DOI：
10.1073/pnas.96.6.3200
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发表时间：
1999-03-16
影响因子：
11.1
通讯作者：
Dolly, JO
中科院分区：
文献类型：
--
作者：
de Paiva, A;Meunier, FA;Dolly, JO
A型肉毒杆菌神经毒素在神经肌肉连接处阻断乙酰胆碱释放，诱导神经末梢芽形成广泛的网络。单次肌内注射毒素后，通过对小鼠胸锁乳突肌神经末梢对N-（3-三乙基丙基铵）-4-（4-（二丁基氨基）苯乙烯基）二溴吡啶摄取的重复I - ilo成像，在几天内检测到对末端染料刺激摄取的抑制，同时新形成的芽的染色增加。28天后，当神经刺激再次引起肌肉收缩时，只发生有调节的囊泡循环；在芽中[显示含有某些可溶性n -乙基马来酰亚胺敏感因子附着蛋白（SNAREs）和乙酰碱受体]，而不是在亲本末端。因此。此时只有这些芽可能负责神经-肌肉传递。然而，恢复过程的第二个不同阶段随后是囊泡转换到原始末端的回归，同时伴随着当时多余芽的消除。这个扩展和后来的“功能”删除？芽表明它们在瘫痪终板修复中的根本重要性，这一发现对神经再生的重要过程产生了影响。
Blockade of acetylcholine release by botulinum neurotoxin type A at the neuromuscular junction induces the formation of an extensive network of nerve-terminal sprouts. By repeated in I ilo imaging of N-(3-triethyl ammonium propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide uptake into identified nerve endings of the mouse sternomastoid muscle after a single intramuscular injection of the toxin, inhibition of stimulated uptake of the dye at the terminals was detected within a few days, together with an increase in staining of the newly formed sprouts. After 28 days, when nerve stimulation again elicited muscle contraction, regulated vesicle recycling occurred only; in the sprouts [shown to contain certain soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAREs) and to abut acetylholine receptors] and not at the parent terminals. Therefore. only these sprouts could be responsible for nerve-muscle transmission at this time. However, a second, distinct phase of the rehabilitation process followed with a return of vesicle turnover to the original terminals, accompanied by an elimination of the by then superfluous sprouts. This extension and later removal of "functional"? sprouts indicate their fundamental importance in the repair of paralyzed endplates, a finding,vith ramifications for the vital process of nerve regeneration.