Promjene inzulinskog signalnog puta u olfaktornom bulbusu eksperimentalnog štakorskog modela sporadične Alzheimerove bolesti

master's thesis

• Title (english): Tracing the insulin signalling changes in olfactory bulb of the rat model of Alzheimers disease
• Author: Dalia Vađunec
• Mentor: Lidija Bach-Rojecky (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Živka Juričić (član povjerenstva)
• Committee member: Jelena Osmanović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2018-09-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Prema literatumim podacima, olfaktorna disfunkcija navodi se kao najraniji klinički simptom u sporadičnoj Alzheimerovoj bolesti (sAB) i može se povezati s hiperfosforilacijom tau proteina. Budući da u potpunosti nije razjašnjen patofiziološki mehanizam olfaktome disfunkcije u sAB, cilj ovog istraživanja bilo je ispitati mogući odnos u ekspresiji slijedećih proteina: inzulinskog receptora (IR), enzima koji razgrađuje inzulin (IDE), ukupnog tau proteina (t-tau) i fosforiliranog tau proteina (p-tau) u olfaktorskom bulbusu (OFB) u različitim vremenskim periodima i dozama nakon streptozotocin-intracerebroventrikularne (STZ-icv) primjene. STZ-icv je reprezentativni životinjski model sAB. Muškim Wistar štakorima bio je injiciran STZ-icv (0,3 mg/kg, 1,0 mg/kg, 3,0 mg/kg) ili citratni pufer (kontrolna skupina) te su žrtvovani jedan i tri mjeseca nakon tretmana. Ekspresija proteina mjerena je Westem blot metodom. Podaci su analizirani Kruskal-Wallis i Mann-Whitney U testovima (p<0,05). U dozi od 0,3 mg/kg STZ-icv nije nađena promjena ispitivanih proteina nakon oba vremenska perioda. IDE je ostao nepromijenjen u svim dozama nakon oba vremenska perioda. IR je smanjen kod doze od 1,0 mg/kg I mjesec nakon STZ-icv, dok je doza od 3,0 mg/kg prvo povećala ekspresiju IR nakon I mjeseca, a zatim smanjila nakon 3 mjeseca. Nakon 3 mjeseca povećana je ekspresija p-tau/t-tau kod doze od 3,0 mg/kg STZ-icv. Smanjena ekspresija lR u olfaktornom bulbusu može dovesti do hiperfosforilacije tau proteina. Rezultati pružaju bolji uvid u razumijevanje patofizioloških mehanizama koji stoje u pozadini olfaktorne disfunkcije kod sAB. Promjene u olfaktorskom bulbusu trebale bi se dodatno istražiti kao potencijalno mjesto djelovanja lijekova u Alzheimerovoj bolesti.

Abstract (english)

According to literature data, olfactory dysfunction could be one ofthe earliest clinical symptom in Sporadic Alzheimer disease (sAD). The olfact01y dysfunction in AD could be associated with hyperphosphorilation of tau protein. Since exact pathophysiological mechanism of olfactory dysfunction in sAD is not fully understood we aimed this study to investigate possible relationship between changes of insulin receptor (lR), insulin degrading enzyme (IDE), tau (t-tau) and phosphorylated tau (p-tau) in olfactoty bulb (OFB) at different time points and doses after the streptozotocin-intracerebroventricularly (STZ-icv) treatment. STZ-icv is sAD representative animal model. Male Wistar rats were injected with STZ-icv (0.3 mg/kg, I .O mg/kg, 3.0 mg/kg) or vehicle (controls) and sacrificed one and three months after the treatment. Protein expressions of IR, IDE, tau and p-tau in OFB were measured by Western blot method. Data were analyzed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). At the <lose of 0.3 mg/kg no change of expression of investigated proteins were found after both time points. IDE was unchanged in ali applied doses after both time points. lR was decreased at I .O mg/kg only 1 month after STZ-icv, while dose of 3.0 mg/kg first increased lR after I month then decreased fR after 3 months. After 3 months the increment of p-tau/t-tau ratio was found at 3.0 mg/kg STZ-icv. Decreased IR could lead to the increased tau phosphorylation in olfactory bulb. These results can provide better understanding of pathophysiological mechanism behind the olfactory dysfunction in sAD. The changes in olfactory bulb should be further explored as potential place for drug targeting in Alzheimer's disease.

• Keywords: Alzheimerova bolest; inzulinski receptor; tau protein; olfaktorni bulbus
• Keywords (english): Alzheimer disease; insulin receptor; tau protein; olfactory bulb
• Language: croatian
• URN:NBN: urn:nbn:hr:163:084701
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-09-06 15:20:21