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

On formation, these sprouts acquire the ability to mediate stimulated vesicle turnover and, at the onset of recovery of nerve-induced muscle twitch, exoendocytosis occurs only within these sprouts and not in the parent terminals

A. de Paiva


Scholarcy highlights

  • The ability of nerve endings at the neuromuscular junction to sprout after the potent blockade of neurotransmission by botulinum neurotoxin type A is a striking example of synaptic plasticity
  • Despite the extent of the paralysis induced by this toxin, recovery of neurotransmission does occur eventually, as manifested in animal experiments and in the clinical treatment of dystonias involving involuntary movement of certain skeletal muscles (see ref
  • Limitations encountered in earlier studies on this fundamentally important question originated from the need to employ conventional histological techniques in vitro to excised tissues. These limitations have been overcome in our study by using high-sensitivity computer-controlled video microscopy to perform repeated imaging of fluorescently labeled nerve endings in living mice
  • Been concluded that the sprouts are formed to release ACh and induce electrical activity that is thought to be essential for the dynamic interplay between motor nerves and nonneuronal cells that aid the implementation of a full recovery from paralysis
  • To allow a direct correlation between these visualized features and the time at which neurotransmission resumes in previously paralyzed muscle, an evaluation of nerve-induced muscle contraction after supramaximal electrical stimulation of the spinal accessory nerve innervating the sternomastoid fibers was made when imaging these nerve endings in living mice
  • Imaging the individually unique nerve endings on the sternomastoid fibers immediately before injection of BoTxA indicated colocalization of 4-di-2-ASP and activity-dependent staining with FM1-43
  • We have shown that after a brief supplementary augmentation of the functional processes subsequent to the onset of recovery of nerve-induced muscle twitch, an eventual cessation of their outgrowth ensues and, on the eventual return of exoendocytosis to the original terminals, the sprouts gradually lose their ability to perform endocytosis for FM1-43 and, shortly thereafter, start to regress

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