title: Botulinum toxin's axonal transport from periphery to the spinal cord.
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.
authors.affiliation: Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Ivica
authors.initials: I
authors.lastname: Matak
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Lacković
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D006614:Hindlimb / Q000502:physiology; D007150:Immunohistochemistry; D007267:Injections; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D018613:Microscopy, Confocal; D009046:Motor Neurons / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D002795:Choline O-Acetyltransferase; D019274:Botulinum Toxins, Type A; D003078:Colchicine