Potencijalno neuroprotektivno djelovanje dehidroepiandrosterona (DHEA) i njegovog sulfata (DHEAS) u modelu ozljede mozga

master's thesis

• Title (english): Potential neuroprotective effects of dehydroepiandsterone (DHEA) and its sulphate (DHEAS) in brain injury model
• Author: Suzana Blažanović
• Mentor: Matea Nikolac Perković (mentor)
• Mentor: Sofia Ana Blažević (sumentor)
• Committee member: Sofia Ana Blažević (predsjednik povjerenstva)
• Committee member: Inga Urlić (član povjerenstva)
• Committee member: Antun Alegro (član povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Neurosteroid dehidroepiandrosteron (DHEA) ključan je u modulaciji neurogeneze,
metabolizma neurona i njihovog preživljenja, a uključen je i u regulaciju važnih moždanih
funkcija poput neuralne plastičnosti, učenja, pamćenja i ponašanja. Dosadašnja istraživanja
pokazala su da DHEA i njegov sulfat (DHEAS) ublažavaju posljedice ekscitotoksičnosti i
oštećenja prouzrokovanih oksidativnim stresom te imaju potencijalno protektivno djelovanje u
slučaju ishemijske ozljede mozga. Deprivacija glukoze, smanjen protok krvi te hipometabolizam
glukoze povezuju se s degeneracijom i smrti neurona kod ishemijskog moždanog udara, ali i kod
neurodegenerativnih bolesti kao što su Alzheimerova te Parkinsonova bolest. Sve navedeno
upućuje na to da bi DHEA i DHEAS mogli biti obećavajući kandidati za istraživanja usmjerena
prema zaštiti neurona, odnosno prema smanjenju oštećenja i odumiranja neurona koji prate
različita akutna stanja, kronične neurodegenerativne bolesti te normalno starenje. Cilj ovog
diplomskog rada je istražiti i razjasniti potencijalne učinke neurosteroida DHEA i DHEAS u
prevenciji neuronske smrti i promicanju preživljavanja neurona uporabom in vitro pristupa,
odnosno uporabom modela deprivacije kisika i glukoze, te reperfuzije (OGD/R) koji vrlo dobro
oponaša ishemijske uvjete i s tim povezana patološka stanja. Rezultati istraživanja upućuju na to
da ispitivani neurosteroidi imaju potencijal u liječenju i prevenciji ozljeda izazvanih ishemijom,
kao i onih uzrokovanih neurodegeneracijom.

Abstract (english)

The neurosteroid dehydroepiandrosterone (DHEA) is crucial in modulating neurogenesis,
neuronal metabolism, and survival, and is involved in the regulation of important brain functions
such as neural plasticity, learning, memory, and behavior. Previous research has shown that
DHEA and its sulfate (DHEAS) alleviate the effects of excitotoxicity and damage caused by
oxidative stress and have potentially protective effects in the case of ischemic brain injury.
Glucose deprivation, decreased blood flow and glucose hypometabolism are associated with
degeneration and death of neurons in ischemic stroke, but also in neurodegenerative diseases
such as Alzheimer's and Parkinson's disease. All of the above suggests that DHEA and DHEAS
could be promising candidates for research aimed at protecting neurons, i.e. reducing the damage
and death of neurons that accompany various acute conditions, chronic neurodegenerative
diseases and normal aging. The aim of this thesis is to investigate and clarify the potential effects
of the neurosteroid DHEA and DHEAS in preventing neuronal death and promoting neuronal
survival using an in vitro approach, i.e. using a model of oxygen and glucose deprivation and
reperfusion (OGD/R) that mimics very well ischemic conditions and related pathological
conditions. Pretreatment and posttreatment with DHEA (S) proved to be neuroprotective. The
results of the study suggest that the studied neurosteroids have potential in the treatment and
prevention of injuries caused by ischemia, as well as those caused by neurodegeneration.

• Keywords: moždani udar; demencija; ishemijsko - reperfuzijska ozljeda; neurosteroidi; humane neuroblastoma stanice; mišji neuroni
• Keywords (english): stroke; dementia; ischemic - reperfusion injury; neurosteroids; human neuroblastoma cells; mouse neurons
• Language: croatian
• URN:NBN: urn:nbn:hr:217:507952
• 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: 2021-07-23 10:33:38