Neuroprotektivni potencijal moždanog neurotrofnog čimbenika u modelu Alzheimerove bolesti in vitro

master's thesis

• Title (english): The neuroprotective potential of brain-derived neurotrophic factor in an in vitro model of Alzheimer's disease
• Author: Katarina Štulić
• Mentor: Gordana Nedić Erjavec (mentor)
• Mentor: Julija Erhardt (sumentor)
• Committee member: Julija Erhardt (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Nada Oršolić (član povjerenstva)
• Committee member: Sandra Hudina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-06-08, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Alzheimerova bolest (AB) je neurodegenerativna bolest koju karakterizira izvanstanično
nakupljanje amiloidnih plakova i unutarstanično nakupljanje neurofibrilarnih snopića. Moždani
neurotrofni čimbenik (BDNF) je najrašireniji neurotrofni čimbenik rasta u središnjem živčanom
sustavu. Eksprimira se u hipokampusu, korteksu i bazalnom prednjem mozgu, područjima koja
su vitalna za učenje, pamćenje i izvršnu funkciju. Primarna uloga BDNF-a u mozgu je
promicanje preživljavanja postmitotskih neurona te rast i diferencijacija novih neurona i sinapsi.
Dosadašnja istraživanja ukazuju na ulogu smanjene razine BDNF-a u AB-u gdje su gubitak
sinapsi i neurona te oslabljeno pamćenje bitan dio patologije. Beta amiloid (Aβ) utječe na razine
BDNF-a direktno, inhibicijom proteolitičke konverzije prekursora u konačnu formu te indirektno
– interferencijom s aksonalnim transportom. S obzirom na zaštitne učinke BDNF-a na
neurotoksičnost izazvanu Aβ u uvjetima in vitro i in vivo, primjena BDNF-a predstavlja
potencijalnu strategiju liječenja AB-a. Cilj ovog rada je ispitati potencijalni učinak BDNF-a u
prevenciji stanične smrti, odnosno promicanju preživljenja neurona, primjenom primarne kulture
mišjih neurona tretiranih oligomerima Aβ kao in vitro modelom AB-a. Rezultati istraživanja
potvrđuju neuroprotektivno djelovanje BDNF-a te upućuju na to da njegova primjena smanjuje
apoptotsku aktivnost u modelu AB-a in vitro.

Abstract (english)

Alzheimer's disease (AD) is a neurodegenerative disease characterized by extracellular
accumulation of amyloid plaques and intracellular accumulation of neurofibrillary tangles. Brain
derived neurotrophic factor (BDNF) is the most abundant neurotrophic growth factor in the central
nervous system. It is expressed in the hippocampus, cortex and basal forebrain, areas vital
for learning, memory and executive function. The primary role of BDNF in the brain is to
promote the survival of postmitotic neurons and the growth and differentiation of new neurons and
synapses. Previous studies suggest the role of decreased BDNF levels in AD, where synapse and
neuron loss and impaired memory are an essential part of the pathology. Amyloid beta (Aβ)
affects BDNF levels directly, by inhibiting the proteolytic conversion of precursors to the final
form, and indirectly by interfering with axonal transport. Given the protective effects of BDNF on
neuronal toxicity induced by Aβ in vitro and in vivo, the use of BDNF represents a potential strategy
for the treatment of AD. The aim of this study was to examine the potential effect of BDNF in the
prevention of cell death, i.e. promoting the survival of neurons, using a primary culture of mouse
cortical neurons treated with Aβ oligomers as an in vitro model of AD. The results of the study
confirm the neuroprotective effect of BDNF and suggest that its use reduces apoptotic activity in
an in vitro model of AD.

• Keywords: demencija; moždani neurotrofni čimbenik; oligomeri beta amiloida; primarna kultura kortikalnih neurona miša; vijabilnost; cistotoksičnost; kaspazna aktivnost
• Keywords (english): dementia; brain derived neurotrophic factor; amyloid beta oligomers; primary culture of mouse cortical neurons; viability; cytotoxicity; caspase activity
• Language: croatian
• URN:NBN: urn:nbn:hr:217:520489
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2024-06-08
• Created on: 2022-07-19 08:36:40