Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida

Bekavac, Ana

prikaz prve stranice dokumenta Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida

Embargo period 2026-01-27

doctoral thesis

Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida

Zagreb: University of Zagreb, School of Medicine, 2025. urn:nbn:hr:105:969378

Bekavac, Ana

University of Zagreb
School of Medicine
Croatian Institiute for Brain Research

Cite this document

APA 6th Edition

Bekavac, A. (2025). Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:969378

MLA 8th Edition

Bekavac, Ana. "Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida." Doctoral thesis, University of Zagreb, School of Medicine, 2025. https://urn.nsk.hr/urn:nbn:hr:105:969378

Chicago 17th Edition

Harvard

Bekavac, A. (2025). 'Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida', Doctoral thesis, University of Zagreb, School of Medicine, accessed 17 March 2025, https://urn.nsk.hr/urn:nbn:hr:105:969378

Vancouver

Bekavac A. Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2025 [cited 2025 March 17] Available at: https://urn.nsk.hr/urn:nbn:hr:105:969378

IEEE

A. Bekavac, "Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2025. Available at: https://urn.nsk.hr/urn:nbn:hr:105:969378

Cite this item: https://urn.nsk.hr/urn:nbn:hr:105:969378

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Title	Istraživanje razvoja kore velikog mozga i neurodegenerativnih promjena u Downovu sindromu na modelu ljudskih cerebralnih organoida
Title (english)	Development of cerebral cortex and neurodegenerative changes in Down syndrome on human cerebral organoids model
Author	Ana Bekavac
Mentor	Dinko Mitrečić (mentor)
Mentor	Ivan Alić (komentor)
Committee member	Nives Pećina-Šlaus (predsjednik povjerenstva)
Committee member	Srećko Gajović (član povjerenstva)
Committee member	Dubravka Švob Štrac (član povjerenstva)
Committee member	Martina Rinčić (član povjerenstva)
Committee member	Miloš Judaš (član povjerenstva)
Granter	University of Zagreb School of Medicine (Croatian Institiute for Brain Research) Zagreb
Defense date and country	2025-01-27, Croatia
Scientific / art field, discipline and subdiscipline	BIOMEDICINE AND HEALTHCARE Basic Medical Sciences Neuroscience
Universal decimal classification (UDC)	61 - Medical sciences
Abstract	Cerebralni organoidi uzgojeni od induciranih pluripotentnih matičnih stanica čovjeka su trodimenzionalne strukture koje rastu oko 100 dana u staničnoj kulturi te razvijaju morfološka obilježja specifična za ljudski mozak. Cilj istraživanja bio je iskoristiti model koji je dobiven od iste osobe, mozaika za trisomiju 21 kromosoma, što omogućava usporedbu diferencijacije kore ljudskog mozga u osoba s Downovim sindromom i njegovom izogeničnom kontrolom. Istraživanje je pokazalo kako cerebralni organoidi čovjeka ispoljavaju sve biljege karakteristične za koru velikog mozga, čime se potvrdila vrijednost ovog modela u istraživanju normalne i narušene strukture mozga. Također pokazano je kako izražaj biljega RELN, CTIP2 i TBR1 kasni u trisomičnim organoidima u odnosu na disomične, što upućuje da kod ljudi s ovom kromosopatijom dolazi do kašnjenja u najranijim fazama razvoja tkiva mozga. Također, zamijećen je manji izražaj svih biljega u trisomičnim organoidima u odnosu na disomične, čime se potvrđuje činjenica kako je cjelokupan broj živčanih stanica u mozgu ljudi s DS smanjen. Nadalje, trisomični organoidi imali su izražene biljege neurodegeneracije 6E10, 4G8 i Aßx-40 čime je potvrđena pretpostavka kako cerebralni organoidi s tri kopije 21 kromosoma predstavljaju koristan model u istraživanju neurodegenerativnih bolesti pridruženih Downovu sindromu, kao što je Alzheimerova demencija. Uspoređujući rezultate na organoidima s rezultatima analize mozgova fetusa s Downovim sindromom, starosti 18.-23. gestacijska tjedna, uočeno je kako organoidi mozga mogu vjerodostojno odražavati zbivanja tijekom embrionalnog razvoja čovjeka.
Abstract (english)	Cerebral organoids grown from human induced pluripotent stem cells are three-dimensional structures that grow for approximately 100 days in cell culture and develop morphological features specific to the human brain. This study aimed to use a model derived from the same individual, a mosaic for trisomy 21, which allowed us to compare cortical differentiation in individuals with Down syndrome and their isogenic control. The study showed that human cerebral organoids express all markers characteristic of the cerebral cortex, confirming the value of this model in studying normal and disrupted brain structure. It was also found that the expression of the RELN, CTIP2, and TBR1 is delayed in trisomic organoids compared to disomic ones, indicating a delay in the earliest stages of brain tissue development in individuals with this chromosomal disorder. Additionally, a lower expression of all markers was observed in trisomic organoids compared to disomic ones, confirming that the total number of neurons in the brains of individuals with Down syndrome is reduced. Furthermore, trisomic organoids exhibited neurodegeneration markers 6E10, 4G8, and Aßx-40, confirming the hypothesis that cerebral organoids with three copies of chromosome 21 are a useful model for studying neurodegenerative diseases, such as Alzheimer's dementia. Comparing the results from the organoids with the results from the analysis of brains of fetuses with Down syndrome, aged 18-23 gestational weeks, it was observed that brain organoids can authentically replicate events that occur during human embryonic development.
Keywords
Keywords (english)
Language	croatian
URN:NBN	urn:nbn:hr:105:969378
Project	Number: DOK-01-2020-111 Title: Antibakterijska prevlaka za biorazgradive medicinske materijale Title: Antibacterial coating for biodegradable medicine materials Acronym: ABBAMEDICA Leader: Iva Rezić Jurisdiction: Croatia Funder: Hrvatska zaklada za znanost Funding stream: Young Researchers’ Career Development Project - Training New Doctoral Students
Project	Number: IP-2022-10-4656 Title: Otkrivanje neurorazvojne osnove Downovog sindroma pomoću jedinstvenih organoida ljudskog mozga Title: Revealing the Neurodevelopmental Basis of Down Syndrome on a Unique Human Brain Organoid Model Acronym: DevDown Leader: Dinko Mitrečić Jurisdiction: Croatia Funder: Hrvatska zaklada za znanost Funding stream: Research Projects
Project	Number: KK.01.1.1.01.0007 Title: Znanstveni centar izvrsnosti - eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi Title: Scientific center of excellence - Experimental and clinical research of hypoxic-ischemic brain damage in perinatal and adulthood Acronym: ZCI-NEURO Leader: Miloš Judaš Jurisdiction: eu Funder: Europska unija Funding stream: European Regional Development Fund
Study programme	Title: Neuroscience Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resource	Text
Extent	125 str.
File origin	Born digital
Access conditions	Embargoed access Embargo expiration date: 2026-01-27
Terms of use
Repository	Dr Med - University of Zagreb School of Medicine Digital Repository
Created on	2025-02-11 12:25:27