Imunohistokemijska i histokemijska obilježja izvanstanične tvari hipokampusa osoba s farmakorezistentnom epilepsijom mezijalnoga temporalnoga režnja

doctoral thesis

• Title (english): Immunohistochemical and histochemical features of hippocampal extracellular matix in patients with drug-resistanat mesial temporal lobe epilepsy
• Author: Barbara Sitaš
• Mentor: Nataša Jovanov Milošević (mentor)
• Mentor: Danijela Kolenc (komentor)
• Committee member: Zdravka Poljaković (predsjednik povjerenstva)
• Committee member: Goran Mrak (član povjerenstva)
• Committee member: Goran Šimić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2023-03-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Izvanstanična tvar (engl. extracellular matrix, ECM) važan je regulator ekscitabilnosti i sinaptičke plastičnosti, posebice u svom kondenziranom obliku, perineuronskim mrežama (PNN). Hipokampalna skleroza tip 1 (HS1) najčešća je patohistološka dijagnoza u bolesnika s farmakorezistentnom epilepsijom mezijalnoga temporalnoga režnja (MTLE). Cilj ovoga rada bio je analizirati sastav ECM-a i njegove promjene u bolesnika koji su kirurški liječeni zbog farmakorezistentne epilepsije mezijalnoga temporalnoga režnja. Uzorci hipokampusa imunohistokemijski su obilježeni i analizirani na sljedeće biljege: agrekan, neurokan, versikan, hondroitin-sulfatne proteeoglikane (CS-56), fibronektin, aglutinin biljke Wisteria Floribunda, NeuN, parvalbumin i glijalni fibrilarni kiseli protein. U uzorcima HS1, osim gubitka neurona i izražene glioze utvrđene su i značajne razlike u ekspresiji veriskana, neurokana, agrekana i WFA-specifične glikozilacije ECM-a uz smanjenje broja perineuronskih mreža. Pacijenti s manjim brojem epileptičnih napadaja imali su manji intenzitet WFA-bojenja u poljima cornu Ammonis (CA). Naši rezultati upućuju na to da razgradanja perineuronskih mreža, zajedno s promjenama u ekspresiji proteina i obrascu glikozilacije ECM-a doprinosi povećanoj ekscitabilnosti piramidnih neurona područja cornu Ammonis i na taj način patofiziologiji i perzistiranju epileptičnih napadaja u farmakorezistentnoj epilepsiji mezijalnoga temporalnoga režnja. Ovo istraživanje implicira da su molekule ECM-a i njihovi modulatori dobri kandidati u razvoju terapijskih pristupa liječenju farmakorezistentne epilepsije.

Abstract (english)

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS-56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic seizures had a less intense diffuse WFA staining in cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons’ excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.

• Keywords: Parvalbumini; Agrekani; Glikozilacija; Hipokampus; Neuroni
• Keywords (english): Parvalbumins; Aggrecans; Glycosylation; Hippocampus; Neurons
• Language: croatian
• URN:NBN: urn:nbn:hr:105:584602
• Project: Number: KK.01.1.1.01.0007; Title: Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi; Leader: Miloš Judaš; Jurisdiction: Croatia; Funder: EK
• Project: Number: IP-2019-04-3182; Title: Moždani izvanstanični matriks u razvitku i perinatalnoj hipoksiji; Title: Brain extracellular matrix in development and in perinatal hypoxia; Acronym: BRAINECM; Leader: Nataša Jovanov Milošević; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Project: Number: 10106-22-3116; Title: Diferencijacija slojeva moždane kore čeonog režnja u razvitku ljudskog mozga; Leader: Nataša Jovanov Milošević; Jurisdiction: Croatia; Funder: HRZZ
• Study programme: Title: Neuroscience; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 82 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-04-06 07:18:35