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master's thesis
Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C
Zagreb: University of Zagreb, Faculty of Science, 2021. urn:nbn:hr:217:538752
Zovko, Ana
University of Zagreb
Faculty of Science
Department of Biology

Institutional repository: Repository of the Faculty of Science

Cite this document

Zovko, A. (2021). Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:538752

Zovko, Ana. "Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C." Master's thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:538752

Zovko, Ana. "Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C." Master's thesis, University of Zagreb, Faculty of Science, 2021. https://urn.nsk.hr/urn:nbn:hr:217:538752

Zovko, A. (2021). 'Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C', Master's thesis, University of Zagreb, Faculty of Science, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:538752

Zovko A. Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2021 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:217:538752

A. Zovko, "Patološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:217:538752

Metadata
TitlePatološke značajke u mozgu miševa nositelja bolesti Niemann-Pick tipa C
Title (english)Pathological features in the brains of mouse carriers of Niemann-Pick type C disease
AuthorAna Zovko
MentorSilva Katušić Hećimović (mentor)
MentorSofia Ana Blažević (sumentor)
Committee memberSofia Ana Blažević (predsjednik povjerenstva)
Committee memberMarija Ivković (član povjerenstva)
Committee memberJulija Erhardt (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Biology)
Zagreb
Defense date and country2021-09-17, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Biology
Abstract
Bolest Niemann-Pick tip C (NPC) rijetka je nasljedna recesivna bolest nakupljanja kolesterola i drugih lipida uslijed disfunkcije proteina NPC1 ili NPC2 koja najčešće pogađa populaciju dječje dobi te za koju još uvijek ne postoji adekvatna terapija. Bolest je uzrokovana mutacijama u NPC1 ili NPC2 genu. Nositelji bolesti koji imaju mutaciju na jednom alelu gena NPC1, do nedavno su se smatrali zdravima. Klinička istraživanja na nositeljima bolesti i na heterozigotnim miševima ukazala su na potencijalne patološke karakteristike NPC bolesti. Cilj ovoga diplomskog rada bio je karakterizirati molekularne procese u mozgovima 100 tjedana starih heterozigotnih NPC1 miševa. Metodom imunohistokemije analiziran je status neuroinflamacije pomoću markera CD68 za mikroglije i GFAP za astrocite. Hiperfosforilacija tau proteina analizirana je metodom Western Blot pomoću antitijela za ukupnu količinu tau proteina i za fosforilirane oblike tau: PHF1, AT8, RZ3 i CP13. U kori velikog mozga i malom mozgu uočena je aktivacija astrocita i mikroglija. Hiperfosforilacija proteina tau zamijećena je uglavnom kod heterozigotnih NPC1 mužjaka, premda se pojavljuje i kod miševa divljeg tipa. Ovaj rad pokazao je da 100-tjedana stari heterozigotni NPC1 miševi pokazuju određene patološke procese karakteristične za bolest NPC, ukazujući na pojavu neuroinflamacije kao začetka neuropatoloških procesa. Istraživanja na mlađim NPC1 heterozigotima neophodna su kako bi se odredila najranija dob pojave neuroinflamacije te istražili potencijali okidači.
Abstract (english)
Niemann-Pick type C (NPC) is a rare hereditary recesive disease characterized by accumulation of cholesterol and other lipids due to NPC1 or NPC2 dysfunction, which mostly affects the population of young childred and with no adequate therapy. NPC is caused by mutations in NPC1 or NPC2 gene. Untill recently disease carriers with mutation on a single NPC1 allele were considered healthy. Rese-arch on NPC1 carriers and heterozygous mice indicated the potential pathological processes caused by NPC1 single allele mutation. The aim of this thesis was to molecularly characterize pathological pro-cesses in the brains of 100-weeks-old heterozygous NPC1 mice. Immunohistochemistry was used to analyze neuroinflammation status using a microglial marker CD68 and an astrocytic marker GFAP. Tau protein hyperphosphorylation was analyzed by Western Blotting using antibodies against „total tau“ and phosphorylated tau: PHF1, AT8, RZ3 and CP13. Activation of microglia and astrocytes was observed in the cortex and cerebellum. Tau hyperphosphorylation was mostly detected in NPC1 hete-rozygous males, yet it appeared within the wild type groupe as well. This work showed that NPC1 heterozygote mouse brains display certain pathological features of NPC disease, with neuroinflamma-tion as a potential initiator of the pathological processes of the disease. Still, research on younger NPC1 heterozygote mice is necessary to determine the earliest age of neuroinflammation and its po-tential triggers.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:538752
Study programmeTitle: Experimental Biology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2023-09-17
Terms of useLicence In copyright icon
Created on2021-09-29 10:11:52