Terapijski potencijal moždanog neurotrofnog čimbenika, neurosteroida dehidroepiandrosterona i dehidroepiandrosteron sulfata u in vitro modelu Parkinsonove bolesti

master's thesis

• Title (english): Therapeutic potential of brain-derived neurotrophic factor, neurosteroid dehydroepiandrosterone and dehydroepiandrosterone sulfate in an in vitro model of Parkinson's disease
• Author: Nora Bacelj
• Mentor: Matea Nikolac Perković (mentor)
• Mentor: Julija Erhardt (komentor)
• Committee member: Julija Erhardt (predsjednik povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Committee member: Zorana Grubić (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Parkinsonova bolest je najčešći neurodegenerativni poremećaj kretanja kojeg karakteriziraju
progresija bolesti te kompleksna klinička slika s motoričkim i ne-motoričkim simptomima.
Neurosteroidi dehidroepiandrosteron (DHEA) i dehidroepiandrosteron sulfat (DHEAS) te
moždani neurotrofni čimbenik (BDNF) ključni su za neuroprotekciju, neurogenezu, memoriju
i učenje te djeluju antioksidativno i protuupalno. Uzimajući u obzir ove činjenice, kao i
činjenicu da trenutno ne postoji lijek za Parkinsonovu bolest, ističe se važnost istraživanja novih
potencijalnih terapeutika poput DHEA, DHEAS i BDNF koji će liječenje učiniti učinkovitijim.
Cilj ovog rada je istražiti potencijalne učinke DHEA, DHEAS i BDNF u prevenciji smrti
dopaminergičkih neurona uporabom in vitro modela, odnosno staničnih linija ozlijeđenih
neurotoksinima rotenonom i 6-hidroksidopaminom koji uzrokuju oštećenja stanica nalik onima
u Parkinsonovoj bolesti. U tu svrhu, provedene su analize vijabilnosti stanica, parametara
oksidativnog stresa te detekcija stanične smrti. Rezultati istraživanja upućuju na to da DHEA,
DHEAS i BDNF pokazuju značajan neuroprotektivni potencijal što se očituje kroz povećanje
preživljavanja stanica te smanjenje razine unutarstaničnih reaktivnih kisikovih jedinki i
apoptotičnih, odnosno nekrotičnih stanica.

Abstract (english)

Parkinson's disease is the most common neurodegenerative movement disorder characterized
by disease progression and a complex clinical picture with motor and non-motor symptoms.
The neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate
(DHEAS) and brain-derived neurotrophic factor (BDNF) are crucial for neuroprotection,
neurogenesis, memory and learning, and have antioxidant and anti-inflammatory effects.
Considering these facts, as well as the fact that there is currently no cure for Parkinson's disease,
the importance of research for new potential therapeutics such as DHEA, DHEAS and BDNF
that will make the treatment more effective is essential. The aim of this thesis is to investigate
the potential effects of DHEA, DHEAS and BDNF in preventing the death of dopaminergic
neurons using in vitro model, i.e. cell lines injured by the neurotoxins rotenone and 6-
hydroxydopamine, which cause cell damage similar to those in Parkinson's disease. For this
purpose, analyzes of cell viability, oxidative stress parameters and detection of cell death were
carried out. Research results indicate that DHEA, DHEAS and BDNF show a significant
neuroprotective potential, which is manifested through an increase in cell survival and a
decrease in the level of intracellular reactive oxygen species and apoptotic and/or necrotic cells.

• Keywords: dopamin; neurodegenerativni poremećaj; neuroprotekcija; neurotoksini; oksidativni stres; stanična smrt
• Keywords (english): dopamine; neurodegenerative disorder; neuroprotection; neurotoxins; oxidative stress; cell death
• Language: croatian
• URN:NBN: urn:nbn:hr:217:094793
• 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: 2022-10-26 11:04:31