Usporedba izraženosti NLRP1 inflamasoma u čeonom režnju zdravih odraslih osoba i bolesnika sa shizofrenijom

master's thesis

• Title (english): Comparison of NLRP1 inflammasome expression in the frontal lobe of healthy adults and patients with schizophrenia
• Author: Dora Vogrinc
• Mentor: Goran Šimić (mentor)
• Committee member: Željka Krsnik (predsjednik povjerenstva)
• Committee member: Zdravko Petanjek (član povjerenstva)
• Committee member: Goran Šimić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Physiology and Immunology); Zagreb
• Defense date and country: 2023-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Physiology

Abstract

Shizofrenija predstavlja jedno od najtežih psihičkih oboljenja koje značajno narušava kvalitetu života pogođene osobe. Ona utječe na sposobnost razmišljanja te iskrivljuje percepciju stvarnosti i subjektivnih iskustava. Etiopatogeneza shizofrenije nije u potpunosti objašnjena te ne postoji općeprihvaćena teorija, no većina dokaza ukazuje na kroničnu neuroinflamaciju kao glavnog faktora koji mijenja funkcioniranje živčanog sustava i uzrokuje psihotične simptome. Stoga je cilj ovog istraživanja bio utvrditi postoji li razlika u izražaju upalnih kompleksa NLRP1 inflamasoma u postmortalnim uzorcima mozga osoba koje boluju od shizofrenije i zdravih kontrola. Analizirani su postmortalni uzorci orbifrontalnog dijela frontalnog režnja mozga sedam osoba oboljelih od shizofrenije (SCH) i pet zdravih kontrola (HC) putem imunohistokemijskog bojenja preparata za NLRP1 protein. Signali u piramidalnim neuronima na obojenim pripravcima manualno su brojani, a zatim su se dijelili s površinom analiziranog područja kako bi se dobila gustoća signala. Usporedbom gustoće, utvrđeno je da je izražaj NLRP1 proteina značajno veći u SCH uzorcima u usporedbi s HC uzorcima. Ovo promatranje dodatno podržava ulogu upale kao ključnog procesa u patogenezi shizofrenije te implicira NLRP1 inflamasom kao potencijalnog medijatora, otvarajući mogućnost istraživanja posebne uloge ovog proteinskog kompleksa u upalnoj patogenezi shizofrenije.

Abstract (english)

Schizophrenia represents one of the most profound psychiatric disorders that greatly compromises the affected individual's overall quality of life. It profoundly impacts cognitive abilities while distorting the perception of reality and subjective experiences. Although a comprehensive understanding of the etiopathogenesis of schizophrenia remains elusive, a prevailing body of evidence indicates a strong association with chronic neuroinflammation, which disrupts the normal functioning of the nervous system and gives rise to psychotic symptoms. Therefore, the primary objective of this investigation was to ascertain whether discrepancies exist in the expression of NLRP1 inflammasome in post-mortem brain specimens obtained from individuals afflicted with schizophrenia, as compared to neurologically healthy controls. Through immunohistochemical staining of the NLRP1 protein, postmortem samples of the orbitofrontal region of the frontal lobe from seven schizophrenia patients (SCH) and five individuals serving as normal controls (HC) were meticulously analysed. Subsequently, the signals within the pyramidal neurons were manually enumerated on the stained preparations and their number was divided by the area of the analysed region, yielding the signal density. By comparing the density measurements, it was established that NLRP1 expression levels were significantly elevated in the samples from individuals with schizophrenia in contrast to those from the healthy control group. This observation provides further support for the involvement of inflammation as a crucial process in the pathogenesis of schizophrenia, thereby implicating the NLRP1 inflammasome as a potential mediator. Consequently, this finding warrants further investigation into the distinct role played by this protein complex in the inflammatory pathogenesis of schizophrenia.

• Keywords: shizofrenija; NLRP1 inflamasom; neuroinflamacija
• Keywords (english): schizophrenia; NLRP1 inflammasome; neuroinflammation
• Language: croatian
• URN:NBN: urn:nbn:hr:105:470803
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-11-02 11:51:41