Naslov
Long-term Motor Central Effects of Botulinum Toxin Type A in Rats

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

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

Izvornik
The 17th International Symposium on Cholinergic Mechanisms, ISCM2022, 8 - 12 May 2022, Dubrovnik / Kovarnik, Zrinka ; Primožič, Ines - , 2022, 75-75

ISBN
978-953-96817-8-2

Skup
17th International Symposium on Cholinergic Mechanisms, ISCM2022

Mjesto i datum
Dubrovnik, Hrvatska, 08.05.2022. - 12.05.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Botulinum toxin type A

Sažetak
Botulinum toxin type A (BoNT-A) is a potent presynaptic neurotoxin and a standard therapy in hyperkinetic movement disorders, presumably due to its local muscular anticholinergic effect. However, recent experimental data point to possible central effects in the CNS. The present 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 TeNT-evoked spastic paralysis. Rats were bilaterally injected with BoNT-A into the gastrocnemius muscle (2 U/kg) or sciatic nerve (5 U/kg). The following day, the animals were injected intrathecally (i.t.) with BoNT-A- neutralizing antitoxin. On day 62, animals were injected i.m. with tetanus neurotoxin (TeNT). 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. BoNT-A reduced the lower hind-limb diameter and muscle size without significant recovery during the entire experiment, which resulted in reduction of CMAP and H reflex. The 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 CMAP, was not affected by the toxin treatment, suggestive of the lack of the toxin’s direct effect on monosynaptic reflex. The enzymatic activity of the toxin, examined by cleaved synaptosomal-associated protein 25 (cSNAP-25) immunohistochemistry, was still present in neuromuscular junctions and spinal cord. The central occurrence of the cSNAP- 25, present in second order spinal cord cholinergic neurons, depended on the toxin’s central transcytosis. 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