Funkcije astrocita u fragilnom X sindromu: in vitro istraživanje

master's thesis

• Title (english): Astroglial function in fragile X syndrome: an in vito investigation
• Author: Darija Begić
• Mentor: Vladimir Mrša (mentor)
• Committee member: Višnja Besendorfer (predsjednik povjerenstva)
• Committee member: Dragomira Majhen (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2022-07-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Fragilni X sindrom (FXS) vodeći je monogenski uzrok poremećaja iz spektra autizma (ASD). Uzrokovan je gubitkom ekspresije FMRP proteina zbog ekspanzije CGG-a. Iako se većina studija usredotočila na uloge FMRP-a u neuronima zbog kognitivnih nedostataka u FXS-u, također se pokazalo da gubitak FMRP-a u astrocitima doprinosi patogenezi FXS-a. Cilj ovog projekta je utvrditi funkcije FMRP-a u astrocitima razvojem strategije prekomjerne ekspresije FMRP-a u astrocitima. U tu svrhu, bila je potrebna karakterizacija astrocita i razvoj učinkovite metode transfekcije. Posebna je pažnja posvećena purinergičkom odgovoru s fokusom na purinergički receptor P2X7. Pokazali smo pojačanu regulaciju purinergičkog odgovora Fmr1 KO astrocita, posebno u pogledu lučenja interleukina-6 (IL-6) nakon tretmana ATP-om. Najučinkovitija i najfleksibilnija metoda transfekcije je magnetofekcija.

Abstract (english)

Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). It is caused by the CGG expansion-induced loss of fragile X mental retardation protein (FMRP) expression. Although most studies focused on the roles of FMRP in neurons due to cognitive deficits in FXS, the loss of FMRP in astroglia has also been shown to contribute to FXS pathogenesis. The aim of this project is to determine the astrocytic functions of FMRP by developing a strategy to overexpress FMRP in astrocytes. To access that, astrocyte characterization and development of an efficient transfection assay were needed. Particular attention was paid to the purinergic response with a focus on the P2X7 purinergic receptor between the C8-D1A cell line and primary astrocytic cell culture (APC). We demonstrated upregulation of the purinergic response of Fmr1 KO astrocytes especially regarding interleukin-6 (IL-6) secretion following ATP treatment. The most efficient and flexible transfection method is magnetofection.

• Keywords: Fragilni X sindrom; FMRP; astrociti; purinergički odgovor; transfekcija
• Keywords (english): Fragile X syndrome; FMRP; astrocytes; purinergic pathways; transfection
• Language: croatian
• URN:NBN: urn:nbn:hr:159:296994
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-04-08 10:33:16