Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission

Meunier, FA, Schiavo, G and Molgo, J (2002) Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission. Journal of Physiology-paris, 96 1-2: 105-113.


Author Meunier, FA
Schiavo, G
Molgo, J
Title Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission
Journal name Journal of Physiology-paris   Check publisher's open access policy
ISSN 0928-4257
Publication date 2002
Sub-type Article (original research)
DOI 10.1016/S0928-4257(01)00086-9
Volume 96
Issue 1-2
Start page 105
End page 113
Total pages 9
Place of publication Paris Cedex 15
Publisher Editions Scientifiques Medicales Elsevier
Language eng
Abstract The neuromuscular junction is one of the most accessible mammalian synapses which offers a useful model to study long-term synaptic modifications occurring throughout life. It is also the natural target of botulinum neurotoxins (BoNTs) causing a selective blockade of the regulated exocytosis of acetylcholine thereby triggering a profound albeit transitory muscular paralysis. The scope of this review is to describe the principal steps implicated in botulinum toxin intoxication from the early events leading to a paralysis to the cellular response implementing an impressive synaptic remodelling culminating in the functional recovery of neuromuscular transmission. BoNT/A treatment promotes extensive sprouting emanating from intoxicated motor nerve terminals and the distal portion of motor axons. The current view is that sprouts have the ability to form functional synapses as they display a number of key proteins required for exocytosis: SNAP-25, VANIP/synaptobrevin, syntaxin-1, synaptotagmin-II, synaptophysin, and voltage-activated Na+, Ca2+ and Ca2+-activated K+ channels. Exo-endocytosis was demonstrated (using the styryl dye FM1-43) to occur only in the sprouts in vivo, at the time of functional recovery emphasising the direct role of nerve terminal outgrowth in implementing the restoration of functional neurotransmitter release (at a time when nerve stimulation again elicited muscle contraction). Interestingly, sprouts are only transitory since a second distinct phase of the rehabilitation process occurs with a return of synaptic activity to the original nerve terminals. This is accompanied by the elimination of the dispensable sprouts. The growth or elimination of these nerve processes appears to be strongly correlated with the level of synaptic activity at the parent terminal. The BoNT/A-induced extension and later removal of "functional" sprouts indicate their fundamental importance in the rehabilitation of paralysed endplates, a finding with ramifications for the vital process of nerve regeneration. (C) 2002 Elsevier Science Ltd. All rights reserved.
Keyword Neurosciences
Physiology
botulinum neurotoxins
neurotransmitter release
neuromuscular junction
FM1-43
exo-endocytosis
sprouting
Motor-nerve Terminals
Gene-related Peptide
Toxin Type-a
Block Neurotransmitter Release
Fast Skeletal-muscle
Tetanus Toxin
Transmitter Release
Brain Synaptosomes
Longus Muscle
Binding-sites
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
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Created: Wed, 17 Oct 2007, 10:59:15 EST