Dugotrajni učinci toksina botulina tipa A na pokazatelje motoričke funkcije u štakora

master's thesis

• Title (english): Long-term effects of botulinum toxin type A on motor performance in rats
• Author: Magdalena Matić
• Mentor: Ivica Matak (mentor)
• Mentor: Dubravka Hranilović (sumentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Duje Lisičić (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-04-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Toksin botulina tipa A (BoNT/A), neurotoksin koji uzrokuje mlohavu paralizu mišića, koristi
se u kontroli nevoljnih pokreta i spazma kod distonija i spasticiteta. Međutim, korisni motorički učinci
kod navedenih poremećaja i njihovo trajanje se ne mogu objasniti isključivim paralitičkim djelovanjem
toksina na neuromuskularne veze, a nedavne studije upućuju na moguće središnje učinke. Stoga smo
ovdje istražili središnje djelovanje toksina na bihevioralne pokazatelje motoričke funkcije. Štakorima je
bilateralno injiciran BoNT-A u m. gastrocnemius (2 U/kg) ili n. ischiadicus (5 U/kg). Za istraživanje
uloge središnje transcitoze BoNT-A u središnje sinapse, životinje su intratekalno injicirane antitoksinom
(5 i.u.). Učinak BoNT-A je ispitivan različitim motoričkim testovima za evaluaciju mlohave paralize,
hoda i plivanja, izdržljivosti, koordinacije, te mišićne atrofije, ali i pomoću imunohistokemijske
detekcije njegovog enzimskog produkta u presjecima leđne moždine. Utvrđeno je da je kombinacija
perifernog i središnjeg učinka BoNT-A intenzivnija i dugotrajnija od njegovog izoliranog perifernog
učinka. Središnji učinci BoNT-A posredovani transcitozom su uglavnom ograničeni na kolinergične
sinapse interneurona leđne moždine. Ovi nalazi upućuju da središnje djelovanje pojačava intenzitet i
produljuje trajanje učinka BoNT-A na motoričke funkcije štakora. Stoga bi dugotrajnost terapijskih
učinaka toksina, gdje je cilj kontrola aktivnosti i tonusa mišića, mogla ovisiti o njegovom središnjem
djelovanju.

Abstract (english)

Botulinum toxin type A (BoNT/A), a neurotoxin that causes flaccid muscle paralysis, is used to
control involuntary movements and spasms in dystonia and spasticity. However, beneficial motor effects
in these disorders and their duration cannot be explained by the exclusive paralytic action of the toxin
on neuromuscular junctions, while recent studies suggest possible central effects. Therefore, here we
investigated the central effect of toxins on behavioral indicators of motor function. Rats were bilaterally
injected with BoNT-A in m. gastrocnemius (2 U/kg) or n. ischiadicus (5 U/kg). To investigate the role
of BoNT-A transcytosis in central synapses, animals were injected intrathecally with antitoxin (5 i.u.).
The effect of BoNT-A was examined by various motor tests to evaluate flaccid paralysis, gait and
swimming, endurance, coordination and muscle atrophy, but also by immunohistochemical detection of
its enzyme product in the spinal cord sections. The combination of the peripheral and central effects of
BoNT-A was found to be more intensive and longer than its isolated peripheral effect. The central effects
of transcytosis-mediated BoNT-A are mainly limited to cholinergic synapses of spinal interneurons.
These findings suggest that the central action intensifies and prolongs the duration of the effect of BoNTA on rat motor functions. Therefore, the longevity of the clinical effects of the toxin and its main
therapeutic goal to control muscle activity and tone could depend on its central action.

• Keywords: središnje djelovanje; transcitoza; atrofija
• Keywords (english): central action; transcytosis; atrophy
• Language: croatian
• URN:NBN: urn:nbn:hr:217:462678
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-05-03 08:24:10