Botulinum toxin's axonal transport from periphery to the spinal cord

Neurochem Int. 2012 Jul;61(2):236-9. doi: 10.1016/j.neuint.2012.05.001. Epub 2012 May 8.

Abstract

Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve. We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 μl). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons. These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport / physiology*
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / metabolism*
  • Choline O-Acetyltransferase / metabolism
  • Colchicine / pharmacology
  • Hindlimb / physiology
  • Immunohistochemistry
  • Injections
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Male
  • Microscopy, Confocal
  • Motor Neurons / metabolism
  • Peripheral Nerves / metabolism*
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / metabolism
  • Sensory Receptor Cells / metabolism
  • Spinal Cord / metabolism*
  • Synaptosomal-Associated Protein 25 / metabolism

Substances

  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Choline O-Acetyltransferase
  • Botulinum Toxins, Type A
  • Colchicine