title: Transsynaptic inhibition of spinal transmission by A2 botulinum toxin.
abstract: Type A botulinum toxin blocks not only ACh release from motor nerve terminals but also central synaptic transmission, including glutamate, noradrenaline, dopamine, ATP, GABA and glycine. Neurotoxins (NTXs) are transported by both antero- and retrogradely along either motor or sensory axons for bidirectional delivery between peripheral tissues or the CNS. A newly developed type A2 NTX (A2NTX) injected into one rat foreleg muscle was transported to the contralateral muscle. This finding was consistent with the NTX traveling retrogradely via spinal neurons and then transsynaptically through motor neurons to the contralateral motor neurons within the spinal cord and on to the soleus muscle. In the present study we found that toxin injection into the rat left soleus muscle clearly induced bilateral muscle relaxation in a dose-dependent fashion, although the contralateral muscle relaxation followed the complete inhibition of toxin-injected ipsilateral muscles. The toxin-injected ipsilateral muscle relaxation was faster and stronger in A2NTX-treated rats than A1LL (BOTOX). A1LL was transported almost equally to the contralateral muscle via neural pathways and the bloodstream. In contrast, A2NTX was mainly transported to contralateral muscles via the blood. A1LL was more successfully transported to contralateral spinal neurons than A2NTX. We also demonstrated that A1LL and A2NTX were carried from peripheral to CNS and vice versa by dual antero- and retrograde axonal transport through either motor or sensory neurons.
authors.affiliation: Research Division for Life Sciences, Kumamoto Health Science University, Kumamoto 861-5598, Japan. akaike@kumamoto-hsu.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akaike
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Shin
authors.forename: Masahito
authors.initials: M
authors.lastname: Wakita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Torii
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Harakawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ginnaga
authors.forename: Keiko
authors.initials: K
authors.lastname: Kato
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
mesh_terms: D000818:Animals; D001904:Botulinum Antitoxin / Q000494:pharmacology; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013376:Substantia Gelatinosa / Q000166:cytology; D013979:Tibial Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D001904:Botulinum Antitoxin; D019274:Botulinum Toxins, Type A; D003078:Colchicine