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

• Published in: Neurochemistry international Vol. 61; no. 2; pp. 236 - 239
• Main Authors: Matak, Ivica, Riederer, Peter, Lacković, Zdravko
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-07-2012; Elsevier
• Subjects: Animals; Axonal transport; Axonal Transport - physiology; Biological and medical sciences; Botulinum toxin; Botulinum toxin A; Botulinum Toxins, Type A - administration & dosage; Botulinum Toxins, Type A - metabolism; Central nervous system; Choline O-Acetyltransferase - metabolism; Cholinergic nerves; Cholinergic neurons; Colchicine; Colchicine - pharmacology; Dorsal horn; Fundamental and applied biological sciences. Psychology; Hindlimb - physiology; Immunohistochemistry; Injections; Injections, Intramuscular; Injections, Subcutaneous; Limbs; Male; Microscopy, Confocal; Motor Neurons - metabolism; Nuclear transport; Peripheral nerve; Peripheral Nerves - metabolism; Rats; Rats, Wistar; Retrograde axonal transport; Sciatic nerve; Sciatic Nerve - metabolism; Sensory Receptor Cells - metabolism; SNAP-25 protein; Spinal cord; Spinal Cord - metabolism; Synaptosomal-associated protein 25; Synaptosomal-Associated Protein 25 - metabolism; Trigeminal nerve; Ventral horn; Vertebrates: nervous system and sense organs; PBS; Botulinum toxin A; Immunohistochemistry; Peripheral nerve; Retrograde axonal transport; Spinal cord; SDS; i.n; s.c; i.m; Synaptosomal-associated protein 25; GFAP; BTX-A; BTX-E; ChAT; NGS; Cholinergic neurons; SNAP-25; Cholinergic neuron; Enzyme; Biological transport; Central nervous system; Metalloendopeptidases; Protein; Peptidases; Bontoxilysin; Synaptosome; Hydrolases
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2012.05.001

Occurrence of cleaved SNAP-25 in ipsilateral lumbal ventral horn following botulinum toxin A (30U/kg) subcutaneous injection into the rat hind paw. [Display omitted]
► Peripheral BTX-A cleaves SNAP-25 in dorsal and ventral horn of the spinal cord. ► Axonal transport of BTX-A occurs at low intramuscular dose. ► BTX-A retrograde transport occurs via peripheral nerves and is microtubule-dependent. ► Truncated SNAP-25 is localized within cholinergic neurons of the ventral horn.
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 (5U/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 (5mM, 2μl). 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.