Recovery of mouse neuromuscular junctions from single and repeated injections of botulinum neurotoxin A.
Recovery of mouse neuromuscular junctions from single and repeated injections of botulinum neurotoxin A.
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DOI：
10.1113/jphysiol.2008.153569
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Slater CR
中科院分区：
文献类型：
--
作者：
Rogozhin AA;Pang KK;Bukharaeva E;Young C;Slater CR
A 型肉毒杆菌神经毒素 (BoNT/A) 通过阻止运动神经末梢释放乙酰胆碱 (ACh) 来麻痹肌肉。尽管毒性很大，但它在临床上用于削弱收缩不良的肌肉，如肌张力障碍。注射 BoNT/A 的效果会在 3-4 个月后消失，因此经常需要重复注射。神经肌肉传递的恢复伴随着运动轴突芽的形成，其中一些形成新的突触接触。然而，这些新接触的功能重要性尚不清楚。使用细胞内和局灶性细胞外记录，我们发现在小鼠滑车上肌 (ETA) 中，一旦新的突触接触就可以检测到原始神经肌肉接头 (NMJ) 区域的量子释放，并且通常占总释放的 80% 以上。在恢复过程中，突触延迟以及终板电位 (EPP) 的上升和衰减时间延长约 3 倍，但在 2-3 个月后恢复正常。 3-4 个月后进行研究时，对频率高达 100 Hz 的重复刺激的反应是正常的。当间隔 3-4 个月注射两次或三次 BoNT/A 时，量子释放恢复正常值的速度比单次注射后更慢（11 和 15 周达到对照值的 50%，而单次注射后 6 周）。此外，肌内肌肉运动轴突的分支、NMJ 的分布和许多个体 NMJ 的结构仍然异常。这些发现强调了哺乳动物 NMJ 的可塑性，但也表明了它的重要局限性。
Botulinum neurotoxin type A (BoNT/A) paralyses muscles by blocking acetylcholine (ACh) release from motor nerve terminals. Although highly toxic, it is used clinically to weaken muscles whose contraction is undesirable, as in dystonias. The effects of an injection of BoNT/A wear off after 3–4 months so repeated injections are often used. Recovery of neuromuscular transmission is accompanied by the formation of motor axon sprouts, some of which form new synaptic contacts. However, the functional importance of these new contacts is unknown. Using intracellular and focal extracellular recording we show that in the mouse epitrochleoanconeus (ETA), quantal release from the region of the original neuromuscular junction (NMJ) can be detected as soon as from new synaptic contacts, and generally accounts for > 80% of total release. During recovery the synaptic delay and the rise and decay times of endplate potentials (EPPs) become prolonged approximately 3-fold, but return to normal after 2–3 months. When studied after 3–4 months, the response to repetitive stimulation at frequencies up to 100 Hz is normal. When two or three injections of BoNT/A are given at intervals of 3–4 months, quantal release returns to normal values more slowly than after a single injection (11 and 15 weeks to reach 50% of control values versus 6 weeks after a single injection). In addition, branching of the intramuscular muscular motor axons, the distribution of the NMJs and the structure of many individual NMJs remain abnormal. These findings highlight the plasticity of the mammalian NMJ but also suggest important limits to it.
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影响因子：
56.9
作者：
Dong, M;Yeh, F;Chapman, ER
通讯作者：
Chapman, ER
影响因子：
5.5
作者：
BROWN, MC;HOLLAND, RL;IRONTON, R
通讯作者：
IRONTON, R
影响因子：
3.4
作者：
CARDASIS, CA;LAFONTAINE, DM
通讯作者：
LAFONTAINE, DM
DOI：
10.1098/rspb.1966.0008
发表时间：
1966-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BARKER, D;IP, MC
通讯作者：
IP, MC
影响因子：
11
作者：
DUCHEN, LW
通讯作者：
DUCHEN, LW