Ekspresija proteina neuroplastina i kalcijske ATP-aze stanične membrane u mišjem modelu neurodegeneracije

master's thesis

• Title (english): Protein neuroplastin and plasma membrane calcium ATP-ase expression in a mouse model of neurodegeneration
• Author: Antonia Oršulić
• Mentor: Katarina Ilić (mentor)
• Mentor: Dubravka Hranilović (sumentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-07-06, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Neuroplastini imaju ulogu u rastu neurita, modulaciji dugoročne sinaptičke plastičnosti, ekscitaciji neurona te regulaciji kalcijske ATP-aze stanične membrane PMCA (od engl. Plasma membrane calcium ATP-ase) i posljedično razine unutarstaničnog kalcija. Promjena ekspresije neuroplastina i s njim povezane PMCA, dovode do poremećene stanične signalizacije ovisne o kalciju čime se narušava razvoj mreţe neurona, smanjuje se oslobađanje neurotransmitera i nemogućnosti odrţavanja molekularnih mehanizama odgovornih za učenje i pamćenje što moţe biti podloga neurodegenerativnih promjena u Alzheimerovoj bolesti. U ovom diplomskom radu istraţeno je dolazi li do promjene ekspresije neuroplastina i PMCA u neurodegeneraciji u različitim regijama mozga u dvije starosne skupine miševa. Na tkivu mozgova miševa divljeg tipa i 5xFAD, modela za obiteljsku Alzheimerovu bolest, imunohistokemijski je određena lokalizacija i analizirana ekspresija oba proteina u tri moţdane regije: hipokampusu, malome mozgu i moţdanoj kori, te je kvantificirana razlika u ekspresiji. Preklapanjem imunofluorescentnih signala pokazana je kolokalizacija neuroplastina i PMCA u svim regijama mozga što upućuje na povezanost neuroplastina s ekspresijom i membranskim pozicioniranjem PMCA. Ekspresija neuroplastina i PMCA u modelu 5xFAD je manji u kori velikog mozga i hipokampusu u odnosu na divlji tip što moţe biti molekularna osnova za poremećaj procesa pamćenja.

Abstract (english)

Neuroplastins play a role in neurite outgrowth, modulation of long-term synaptic plasticity, neuronal excitation, regulation of plasma membrane calcium ATPase (PMCA) and consequently intracellular calcium levels. Alterations in neuroplastin and PMCA expression lead to impaired calcium-dependent cellular signaling and consequently to impaired neuronal network development, decreased neurotransmitter release, and the inability to sustain the molecular mechanisms responsible for learning and memory which could underlie the neurodegenerative mechanisms of Alzheimer's disease. In this work, we investigated whether there is a change in neuroplastin and PMCA expression in neurodegeneration in different brain regions and two age groups of mice. In brain tissue from wild-type mice and 5xFAD, a model for familial Alzheimer's disease, immunohistochemistry was used to determine the localization and expression of both proteins in three brain regions: hippocampus, cerebellum and cerebral cortex, and the difference in expression was quantified. The overlap of immunofluorescence signals showed the colocalization of neuroplastin and PMCA in all brain regions, indicating the association of neuroplastin with the expression and membrane positioning of PMCA. The expression of neuroplastin and PMCA in the 5xFAD model is lower in the cerebral cortex and hippocampus compared to wild type, which may be the molecular basis for the disruption of the memory process.

• Keywords: neuroplastin; PMCA; 5xFAD; neurodegeneracija
• Keywords (english): Neuroplastin; PMCA; 5xFAD; neurodegeneration
• Language: croatian
• URN:NBN: urn:nbn:hr:217:962347
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-07-06
• Created on: 2021-07-22 10:07:23