Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals

Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3200-5. doi: 10.1073/pnas.96.6.3200.

Abstract

Blockade of acetylcholine release by botulinum neurotoxin type A at the neuromuscular junction induces the formation of an extensive network of nerve-terminal sprouts. By repeated in vivo imaging of N-(3-triethyl ammonium propyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide uptake into identified nerve endings of the mouse sternomastoid muscle after a single intramuscular injection of the toxin, inhibition of stimulated uptake of the dye at the terminals was detected within a few days, together with an increase in staining of the newly formed sprouts. After 28 days, when nerve stimulation again elicited muscle contraction, regulated vesicle recycling occurred only in the sprouts [shown to contain certain soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAREs) and to abut acetylcholine receptors] and not at the parent terminals. Therefore, only these sprouts could be responsible for nerve-muscle transmission at this time. However, a second, distinct phase of the rehabilitation process followed with a return of vesicle turnover to the original terminals, accompanied by an elimination of the by then superfluous sprouts. This extension and later removal of "functional" sprouts indicate their fundamental importance in the repair of paralyzed endplates, a finding with ramifications for the vital process of nerve regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / poisoning*
  • Female
  • Fluorescent Dyes
  • Male
  • Membrane Proteins / physiology
  • Mice
  • Motor Endplate / drug effects*
  • Motor Endplate / physiopathology*
  • Neuromuscular Junction / drug effects*
  • Neuromuscular Junction / physiopathology*
  • Neuronal Plasticity*
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • SNARE Proteins
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Vesicular Transport Proteins*

Substances

  • Fluorescent Dyes
  • Membrane Proteins
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • SNARE Proteins
  • Vesicular Transport Proteins
  • Botulinum Toxins, Type A