Uloga kortikalnih interneurona u patogenezi shizofrenije

master's thesis

• Title (english): Role of cortical interneurons in pathogenesis of schizophrenia
• Author: Matija Vid Prkačin
• Mentor: Ana Hladnik (mentor)
• Committee member: Fran Borovečki (predsjednik povjerenstva)
• Committee member: Dražen Begić (član povjerenstva)
• Committee member: Ana Hladnik (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Anatomy and Clinical Anatomy); Zagreb
• Defense date and country: 2020-07-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy

Abstract

Shizofrenija je psihijatrijska bolest koja se manifestira raznim simptomima poput deluzija, halucinacija i socijalnog udaljavanja. Iako je istraživački interes oko shizofrenije velik, te se u zadnjih nekoliko godina javio velik napredak u znanosti i tehnikama proučavanja mozga, znanstvenici i dalje nisu uspjeli definirati točne mehanizme nastanka shizofrenije. Jedan od potencijalnih mehanizama patogeneze shizofrenije je disfunkcija kortikalnih interneurona, odnosno disfunkcija sustava glavnog interneurona kojeg oni luče – gama-aminomaslačne kiseline (GABA-e). Studije rađene na osobama oboljelim od shizofrenije pružaju razne nalaze koji bi podupirali hipotezu da disfunkcija kortikalnih interneurona vodi raznim mehanizmima do razvoja shizofrenije. Nađen je smanjen broj sinapsi na tijelima kortikalnih interneurona (smanjen je input), nađena je manja količina enzima koji sintetiziraju GABA-u kao i njihove kodirajuće mRNA. Također su nađene i promijenjene količine GABA receptora u sinapsama koje kortikalni interneuroni čine (smanjen im je output). Slikovne metode prikaza mozga također ukazuju na određene abnormalnosti što se tiče morfologije, ali i funkcije određenih moždanih regija kod osoba oboljelih od shizofrenije. Takva saznanja bi jednog dana mogla imati klinički značaj u smislu detekcije patološki promijenjenih regija mozga koje bi trebale biti mjesto ciljane terapije.

Abstract (english)

Schizophrenia is a psychiatric disease that manifests with various symptoms, such as delusions, hallucinations and social withdrawal. Although research interest in schizophrenia is high, scientists are still unable to define exact mechanisms that lead to the development of the disease, in spite of breakthroughs in scientific methods. One of the potential pathogenetic mechanisms involves dysfunction of cortical inter-neurons, more precisely dysfunction of their main neurotransmitter – gamma-aminobutyric acid (GABA). Studies performed on patients suffering from schizophrenia offer some evidence that
support the hypothesis that dysfunction of cortical interneurons leads to development of schizophrenia through various mechanisms. Decreased number of synapses on the membrane of cortical interneurons was found (lower input), followed with the decreased number of enzymes that lead to the GABA production as well as their encoding mRNA. Moreover, a decrease in GABA receptor density was found in synapses involving cortical interneurons (decreased output). Imaging methods also provide findings of abnormalities in both morphology and function of several regions of the brain in patients suffering schizophrenia. Such findings could potentially have therapeutic value in the future in means of highlighting pathological regions of the brain that should be a therapeutic target.

• Keywords: interneuron; shizofrenija; GABA
• Keywords (english): interneuron; schizophrenia; GABA
• Language: croatian
• URN:NBN: urn:nbn:hr:105:826371
• 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: 2021-03-03 09:45:30