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ID 114463
タイトル別表記
Central effects of botulinum toxins
著者
Koizumi, Hidetaka University of Tokushima
Akaike, Norio Kumamoto Health Science University
Torii, Yasushi The Chemo-Sero-Therapeutic Research Institute|Osaka University
Harakawa, Tetsuhiro The Chemo-Sero-Therapeutic Research Institute
Ginnaga, Akihiro The Chemo-Sero-Therapeutic Research Institute
キーワード
botulinum neurotoxin
spinal cord
central effects
SNAP-25
axonal transport
資料タイプ
学術雑誌論文
抄録
Because of its unique ability to exert long-lasting synaptic transmission blockade, botulinum neurotoxin A (BoNT/A) is used to treat a wide variety of disorders involving peripheral nerve terminal hyperexcitability. However, it has been a matter of debate whether this toxin has central or peripheral sites of action.We employed a rat model in which BoNT/A1 or BoNT/A2 was unilaterally injected into the gastrocnemius muscle. On time-course measurements of compound muscle action potential (CMAP) amplitudes after injection of BoNT/A1 or BoNT/A2 at doses ranging from 1.7 to 13.6U, CMAP amplitude for the ipsilateral hind leg was markedly decreased on the first day, and this muscle flaccidity persisted up to the 14th day. Of note, both BoNT/A1 and BoNT/A2 administrations also resulted in decreased CMAP amplitudes for the contralateral leg in a dose-dependent manner ranging from 1.7 to 13.6U, and this muscle flaccidity increased until the fourth day and then slowly recovered. Immunohistochemical results revealed that BoNT/A-cleaved synaptosomal-associated protein of 25 kDa (SNAP-25) appeared in the bilateral ventral and dorsal horns 4 days after injection of BoNT/A1 (10 U) or BoNT/A2 (10 U), although there seemed to be a wider spread of BoNT/A-cleaved SNAP-25 associated with BoNT/A1 than BoNT/A2 in the contralateral spinal cord. This suggests that the catalytically active BoNT/A1 and BoNT/A2 were axonally transported via peripheral motor and sensory nerves to the spinal cord, where they spread through a transcytosis (cell-to-cell trafficking) mechanism. Our results provide evidence for the central effects of intramuscularly administered BoNT/A1 and BoNT/A2 in the spinal cord, and a new insight into the clinical effects of peripheral BoNT/A applications.
掲載誌名
Frontiers in Neurology
ISSN
16642295
出版者
Frontiers Media S.A.
5
開始ページ
98
発行日
2014-06-23
権利情報
©2014 Koizumi, Goto, Okita, Morigaki, Akaike, Torii, Harakawa, Ginnaga and Kaji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CCBY)(https://creativecommons.org/licenses/by/3.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系
病院