Naslov
Retrograde axonal transport of botulinum toxin A in rat spinal motoneurons: an immunohistochemical study

Autori
Matak, Ivica ; Lacković, Zdravko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum Biologorum - Vol 112, Suppl 1 / Branko Vitale - Zagreb : Hrvatsko prirodoslovno društvo, 2010, 89-89

Skup
6. Hrvatski farmakološki kongres s međunarodnim sudjelovanjem

Mjesto i datum
Opatija, Hrvatska, 15.09.2010. - 18.09.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
botulinum toxin type A; spinal motoneurons; axonal transport
(botulinum toxin type A; spinal motoneurons; axonal transpor)

Sažetak
Introduction: Botulinum toxin type A (BTX-A) is widely used as a treatment for various types of muscular overactivity disorders like focal dystonia and spasticity, presumably due to its neuromuscular blocking properties exerted by peripheral SNAP-25 cleavage. However, recently, retrograde axonal transport of Botulinum toxin A has been demonstrated by immunohistochemistry (Antonucci et al, J Neurosci 28 ; 2008:3689) and behavioral experients (Bach-Rojecky & Lacković, Pharmacol Biochem Behav. 94 ; 2009:234). Here we demonstrate the cleavage of central SNAP-25 in spinal cord ventral horns after single peripheral BTX-A administration. Materials and methods: Male Wistar rats were injected unilaterally with BTX-A: subcutaneously (s.c.) into the paw pad (30U/kg), intramuscularly (i.m.) into the gastrocnemius (30U/kg), or intraneuronally (i.n.) into the sciatic nerve (10U/kg). The axonal transport blocker colchicin (5 mM) or saline were injected into the sciatic nerve 1 day prior to the more distal i.n. BTX-A injection. 5 days after BTX-A injection rats were transcardially perfused with saline, followed by paraformaldehyde. Lumbal spinal cords were removed and prepared for immunohistochemistry. Spinal cord frozen sections were incubated with anti-BTX-A- cleaved SNAP-25 primary and immunofluorescently labeled secondary antibodies. Results: BTX-A- cleaved SNAP-25 immunoreactivity appeared in ipsilateral ventral horns of s.c., i.m. and i.n.- BTX treated animals. Colchicin abolished the cleaved SNAP-25 immunoreactivity in spinal cord of i.n.- treated animals. Discussion: Both cleavage of central SNAP-25 in spinal cord ventral horns after single peripheral application of BTX-A, and prevention of central SNAP-25 cleavage by colchicin, demonstrate the long-distance axonal traffic of enzymatically active fragments of BTX-A from periphery to the CNS. BTX-A beneficial effects in muscular disorder treatment could be partially mediated by its direct central actions. These results confirm recent findings on retrograde axonal transport of BTX-A (cited above). Acknowledgements: This work was supported by Croatian Ministry of Science, Education and Sport, (Project No. 108- 1080003-0001) and Deutsche Academische Austauch Dienst (DAAD). Antibody to BTX-A–cleaved SNAP-25 was a kind gift from Dr. Ornella Rossetto (University of Padua, Italy).

Izvorni jezik
Engleski

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