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master's thesis
Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti
Zagreb: University of Zagreb, School of Medicine, 2015. urn:nbn:hr:105:818987
Smailović, Una
University of Zagreb
School of Medicine
Department of Pharmacology

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Smailović, U. (2015). Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti (Master's thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:818987

Smailović, Una. "Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti." Master's thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:818987

Smailović, Una. "Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti." Master's thesis, University of Zagreb, School of Medicine, 2015. https://urn.nsk.hr/urn:nbn:hr:105:818987

Smailović, U. (2015). 'Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti', Master's thesis, University of Zagreb, School of Medicine, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:105:818987

Smailović U. Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti [Master's thesis]. Zagreb: University of Zagreb, School of Medicine; 2015 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:105:818987

U. Smailović, "Terapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti", Master's thesis, University of Zagreb, School of Medicine, Zagreb, 2015. Available at: https://urn.nsk.hr/urn:nbn:hr:105:818987

Metadata
TitleTerapijski učinak multifunkcionalnog kelatora željeza M30 u štakorskom modelu sporadične Alzheimerove bolesti
Title (english)Therapeutic effects of multifunctional iron-chelating agent M30 in a rat model of sporadic Alzheimer's disease
AuthorUna Smailović
MentorMelita Šalković-Petrišić (mentor)
Committee memberVLADIMIR TRKULJA (predsjednik povjerenstva)
Committee memberJasenka Markeljević (član povjerenstva)
Committee memberMelita Šalković-Petrišić (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
(Department of Pharmacology)
Zagreb
Defense date and country2015-07-15, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Pharmacology
Abstract
Štakori s intracerebroventrikularnom primjenom streptozotocina (STZ-icv) predloženi su kao model sporadične Alzheimerove bolesti (sAD). Rad je imao za cilj ispitati terapijski potencijal multifunkcionalnog kelatora željeza M30 u STZ-icv štakorskom modelu sAD-a. Odraslim Wistar štakorima je icv injiciran STZ (3 mg/kg) ili citratni pufer (kontrola). Počevši od 8. dana od icv primjene, polovica STZ-icv skupine tretirana je oralno vodom (STZ), druga polovica s M30 (10 mg/kg 3x tjedno) (STZ+M30), te su sve životinje žrtvovane 2 tjedna nakon icv primjene. Ekspresija fosfo tau PHF13 i AT8 proteina te fosfo i ukupne glikogen sintaze kinaze 3β (GSK3β) i ciklin ovisne kinaze 5 (CDK5) mjerena je u hipokampusu pomoću SDS-PAGE. Nakupljanje željeza u mozgu detektirano je histološki bojanjem Berlinskim modrilom. Primjena M30 smanjila je povećanu ekspresiju p-tau-PHF13 (p<0,05) u STZ-icv štakorskom modelu, u usporedbi sa STZ-icv tretiranim štakorima koji su primali samo vodu. Ekspresija/aktivnost AT8 i GSK3β ostala je nepromijenjena u svim grupama. Ekspresija CDK5 bila je značajno niža u STZ i STZ+M30 skupinama, u usporedbi s kontrolom (p<0,05). Primjena M30 značajno je smanjila pozitivan signal patološki nakupljenog željeza u mozgu STZ-icv štakora. Naši rezultati podupiru neuroprotektivnu ulogu multifunkcionalnog kelatora željeza M30 i pružaju dokaze molekularnih mehanizama terapijskog djelovanja M30 u STZ-icv modelu sAD-a.
Abstract (english)
Rats treated intracerebroventricularly with streptozotocin (STZ-icv) have been proposed as a model of sporadic Alzheimer’s disease (sAD). We aimed to assess the therapeutic potential of a novel multifunctional iron-chelating compound M30 in STZ-icv rat model. Adult male Wistar rats were injected icv with STZ (3 mg/kg) or vehicle (control). STZ-icv injected rats were treated orally with water (STZ) or M30 (10 mg/kg 3x a week) starting 8 days after icv treatment (STZ+M30), respectively, and sacrificed 2 weeks after icv treatment. Protein expression of phospho tau protein PHF13 and AT8, phospho and total glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5) in hippocampus was measured by SDS-PAGE. Brain iron levels were detected by Prussian blue iron staining. M30 treatment decreased STZ-icv-induced increment in p-tau PHF13 expression (p<0.05), compared to STZ-icv treatment alone. AT8 and GSK3β expression/activity remained unchanged in all groups. CDK5 expression was found significantly decreased both in STZ and STZ+M30 compared to the control (p<0.05). M30 treatment reduced positive signal of pathological iron accumulation in the STZ-icv rat brain. The results further support the neuroprotective role of multifunctional iron-chelator M30 and provide evidence on the molecular mechanisms of the therapeutic potential of M30 in STZ-icv model of sAD.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:818987
ProjectNumber: MZOŠ 108-1080003-0020
Title: Mozak, eksperimentalni i cerebralni dijabetes i kognitivni i drugi poremećaji
Leader: Melita Šalković-Petrišić
Jurisdiction: Croatia
Funder: MZOŠ
Study programmeTitle: Medicine
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resourceText
File originBorn digital
Access conditionsOpen access
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Created on2016-08-10 08:49:17