Naslov
Central Effects of Botulinum Toxin Type A in Motor Nervous System of the Rat

Autori
Šoštarić, Petra ; Matić, Magdalena ; Matak, Ivica

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

Izvornik
BraYn 2022 5th Brainstorming Research Assembly for Young Neuroscientists, Book of Abstracts / - , 2022, 57-57

Skup
5th Brainstorming Research Assembly for Young Neuroscientists (BraYn)

Mjesto i datum
Rim, Italija, 28.09.2022. - 30.09.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BoNT-A, motoric effects, central action

Sažetak
Botulinum toxin type A (BoNT-A) is a potent neurotoxin with anticholinergic effect. It is a standard therapy in various movement disorders, presumably due to action on local neuromuscular terminals. However, observations in clinics and recent experimental data, points to the possible central effects. The aim was to examine the contribution of the transcytosis-dependent central toxin action on the long term muscular function recovery in rats, as well as tetanus neurotoxin (TeNT) evoked spastic paralysis after peripheral application. Rats were bilaterally injected with BoNT-A into the gastrocnemius muscle (2 U/kg) or sciatic nerve (5 U/kg). To stop the toxin central transcytosis, BoNT-A-neutralizing antitoxin was intrathecally (i.t.) administered after 24 hours. After recovery from flaccid paralysis, TeNT was intramuscularly (i.m.) injected to animals on day 62. In different motor tests (gait ability score, digit abduction score, rota-rod, beam walking and swimming performance), i.t. antitoxin significantly accelerated the flaccid paralysis and motor performance recovery. TeNT-evoked increase in muscle tone was reduced by BoNT-A dependently on its central effect. However, the H-reflex, when corrected for reduced muscle size or reduced compound muscle action potential (CMAP), was not affected by the toxin treatment, suggestive of the lack of the toxin’s direct effect on monosynaptic reflex. The toxin enzymatic activity examined by cleaved synaptosomal-associated protein 25 (cSNAP-25) immunohistochemistry, was still present in neuromuscular junctions and spinal cord. cSNAP-25, presence in second order spinal cord cholinergic neurons, depended on the toxin’s central transcytosis. Conclusion:Long term motor effects of BoNT-A both on normal motor performance (day 1-62), as well as the spastic paralysis (days 62-78), are influenced by the toxin’s ongoing central action mediated by retrograde transport and transcytosis. These data suggest that clinically relevant beneficial effect of BoNT-A result from toxin’s combined peripheral and central effects.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA