prikaz prve stranice dokumenta Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C
Embargo period 2025-02-21
master's thesis
Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C
Zagreb: University of Zagreb, Faculty of Science, 2023. urn:nbn:hr:217:715744
Martinović, Lovro
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Martinović, L. (2023). Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:715744

Martinović, Lovro. "Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C." Master's thesis, University of Zagreb, Faculty of Science, 2023. https://urn.nsk.hr/urn:nbn:hr:217:715744

Martinović, Lovro. "Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C." Master's thesis, University of Zagreb, Faculty of Science, 2023. https://urn.nsk.hr/urn:nbn:hr:217:715744

Martinović, L. (2023). 'Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C', Master's thesis, University of Zagreb, Faculty of Science, accessed 22 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:715744

Martinović L. Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2023 [cited 2024 November 22] Available at: https://urn.nsk.hr/urn:nbn:hr:217:715744

L. Martinović, "Otkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:217:715744

Metadata
TitleOtkrivanje ranih neuropatoloških promjena u miševa prenositelja bolesti Niemann-Pick tipa C
Title (english)Detection of the early neuropathological changes in mice Niemann-Pick type C disease carriers
AuthorLovro Martinović
MentorSilva Katušić Hećimović (mentor)
MentorJulija Erhardt (komentor)
Committee memberJulija Erhardt (predsjednik povjerenstva)
Committee memberInga Urlić (član povjerenstva)
Committee memberPetra Peharec Štefanić (član povjerenstva)
Committee memberMaja Matulić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2023-02-21, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Bolest Niemann-Pick tipa C (NPC) je monogenska, autosomno recesivna, smrtonosna neurodegenerativna bolest, uzrokovana mutacijama u genima NPC1 ili NPC2 koji kodiraju za transportere kolesterola iz kasnih endosoma/lizosoma. Smatralo se da su prenositelji bolesti NPC, koji imaju mutaciju u jednom alelu gena NPC1/2, potpuno zdravi, dok se nisu primijetile određene neuropsihijatrijske promjene u starijoj dobi. Također, istraživanja na mišjem modelu NPC1 heterozigota (NPC1-het) ukazuju na pojavu neurodegeneracije i neuroinflamacije u starijoj dobi. Cilj diplomskog rada bio je utvrditi najranije neuropatološke promjene u prenositelja bolesti NPC, tj. u kori velikog mozga, hipokampusu i malom mozgu 20 i 40 tjedana starih miševa NPC1-het u odnosu na miševe divljeg tipa (WT) iste starosti. Rezultati imunohistokemijske analize hipokampusa pokazuju pojavu aktivacije astrocita (biljeg GFAP) u miševa NPC1-het starih 20 tjedana. Otkriveno je i povećano bojanje lizosoma (biljeg Lamp1) te nakupljanje kolesterola (bojanje filipinom) u miševa NPC1-het starih 20 i 40 tjedana u svim analiziranim moždanim regijama u odnosu na uzorke WT. Dobiveni rezultati ukazuju da bi prenositelji bolesti NPC mogli pokazivati ključne neuropatološke karaktersitike bolesti NPC, uključujući nakupljanje kolesterola, disfunkciju lizosoma i neuroinflamaciju. Daljnja istraživanja su neophodna kako bi se dodatno razjasnile uočene promjene na mišjem kao i na humanom modelu prenositelja bolesti NPC.
Abstract (english)
Niemann-Pick type C disease (NPC) is a monogenic, autosomal recessive, fatal neurodegenerative disorder, caused by mutations in the NPC1 or NPC2 genes that code for cholesterol transport proteins from late endosomes/lysosomes. Carriers of NPC disease, who have a mutation in only one allele of the NPC1/2 genes, were considered healthy, until certain neuropsychiatric changes were recently observed in their old age. Moreover, studies of the aged brains of NPC1 heterozygous mice (NPC1-het) indicated neurodegeneration and neuroinflammation. The aim of this thesis was to investigate the earliest neuropathological changes in carriers of the NPC disease, i.e. in the cerebral cortices, hippocampi and cerebella of 20 and 40-weeks-old NPC1-het mice compared to wild-type (WT) mice of the same age. Immunohistochemical analysis of the hippocampi identified activation of astrocytes (marker GFAP) in 20-weeks-old NPC1-het mice. Increased lysosomal staining (Lamp1 marker) and cholesterol accumulation (filipin staining) were also detected in all analyzed brain regions of 20 and 40-weeks-old NPC1-het mice vs. WT samples. The obtained results indicate that carriers of NPC disease may exert key neuropathological features of NPC disease, including cholesterol accumulation, lysosomal dysfunction and neuroinflammation. Further studies are necessary to elucidate the observed changes in the mouse model as well as the human model of the NPC disease carriers.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:715744
Study programmeTitle: Molecular Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
Type of resourceText
File originBorn digital
Access conditionsEmbargoed access
Embargo expiration date: 2025-02-21
Terms of useLicence In copyright icon
Created on2023-03-01 13:27:35