Botulinum toxin's axonal transport from periphery to the spinal cord
Botulinum toxin's axonal transport from periphery to the spinal cord
复制标题
DOI：
10.1016/j.neuint.2012.05.001
复制
发表时间：
2012-07-01
影响因子：
4.2
通讯作者：
Lackovic, Zdravko
中科院分区：
文献类型：
--
作者：
Matak, Ivica;Riederer, Peter;Lackovic, Zdravko
酶活性肉毒毒素A （BTX-A）从外周到中枢神经系统的轴突运输已在面神经和三叉神经中被描述，导致突触体相关蛋白25 （SNAP-25）在中央核中的分裂。本研究旨在探讨经坐骨神经外周应用BTX-A到脊髓的轴突转运是否存在。后肢肌内注射、皮下注射和坐骨神经内注射BTX-A后，采用BTX-A-cleaved SNAP-25免疫组化对腰椎进行免疫组化。单次外周BTX-A给药后，即使在低肌注剂量（5 U/kg）下，同侧脊髓腹角和背角的SNAP-25也出现截断。在坐骨神经注射BTX-A后，近端腹膜内注射秋水仙碱（5 mM, 2 μ l）可防止SNAP-25在脊髓内出现断裂。利用胆碱-乙酰转移酶（choline-acetyltransferase, ChAT）双标记，将腹角裂解的SNAP-25定位于胆碱能神经元内。这些结果扩展了BTX-A在面神经和三叉神经中轴突逆行转运的最新研究结果。低剂量外周BTX-A后脊髓内SNAP-25出现截短，提示外周应用BTX-A后，轴突转运普遍发生。(C) 2012 Elsevier Ltd.版权所有。
Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve.We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 mu l). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons.These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application. (C) 2012 Elsevier Ltd. All rights reserved.