Modulacija crijevnoga mikrobioma kvercetinom u štakorskomu modelu Alzheimerove bolesti

doctoral thesis

• Title (english): Modulation of intestinal microbiome with quercetin in the rat model of Alzheimer's disease
• Author: Marina Kukolj
• Mentor: Nada Oršolić (mentor)
• Committee member: Jasna Hrenović (predsjednik povjerenstva)
• Committee member: Romana Gračan (član povjerenstva)
• Committee member: Svjetlana Terzić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2020-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 57 - Biological sciences. Physical anthropology. Biodiversity

Abstract

Cilj rada bio je ustanoviti poveznicu između narušene osi crijevna mikrobiota-crijeva-mozak (GBA) i primjene funkcionalne hrane u održavanju mikrobne homeostaze i funkcije središnjeg živčanog sustava (CNS-a) u štakorskomu modelu Alzheimerove bolest (AD). Rezultati ukazuju da kvercetin, kao funkcionalna sastavnica hrane, uspješno modulira narušene homeostatske i neuropatološke posljedice primjene aluminijevog klorida i D-galaktoze tijekom 28 dana: uspješno regulira razinu oksidacijskog stresa i antioksidanata vodeći do izravne zaštite neurona; inhibirajući aktivnost AChE smanjuje agregaciju Aβ; održava razinu BDNF povećavajući preživljavanje, rast i diferencijaciju živčanih stanica; smanjuje razinu nitrita, aktivnosti arginaze i proupalnih citokina regulirajući imunoreaktivnost mikroglija stanica i neuroupalu; održava mikrobnu homeostazu i cjelovitost crijevnoga endotela vodeći očuvanju homeostatskih procesa u CNS-u. Višestruki učinci kvercetina potvrđuju da kvercetin jest funkcionalna sastavnica hrane te može biti primijenjen kao alternativni ne-farmaceutski pristup u održavanju zdravlja i dobrobiti crijeva. Promicanjem crijevne mikrobne homeostaze kvercetin omogućuje održavanje funkcionalnosti CNS-a te cjelokupnog organizma.

Abstract (english)

The aim of this dissertation was to find a link between impaired intestinal microbiome-gut-brain axis (GBA) and the use of quercetin, a functional food component, in maintaining microbial homeostasis and function of central nervous system (CNS) in the rat model of Alzheimer's disease (AD). The results indicate that quercetin successfully modulated impaired homeostatic and neuropathological consequences of aluminium chloride and D-galactose administration over 28 days: it directly protected the neurons by regulating the level of oxidative stress and antioxidants; reduced Aβ aggregation by inhibiting AChE activity; increased nerve cell survival, growth, and differentiation by maintaining BDNF levels; regulated the immunoreactivity of microglia and neuroinflammation by reducing the nitrite levels, arginase activity and proinflammatory cytokines; and maintained microbial homeostasis and intestinal endothelial integrity. The multiple effects confirm that quercetin can be applied as an alternative non-pharmaceutical approach in maintaining intestinal health and microbial homeostasis, which consequently affect the functioning of the CNS and the whole organism.

• Keywords: crijevna mikrobiota; disbioza; aluminijev klorid; kvercetin; Alzheimerova bolest; oksidacijski stres; neuroupala
• Keywords (english): intestinal microbiome; dysbiosis; aluminum chloride; quercetin; Alzheimer's disease; oxidative stress; neuroinflammation
• Language: croatian
• URN:NBN: urn:nbn:hr:217:707173
• Promotion: 2020
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-09-28
• Created on: 2020-10-08 08:56:40