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Effects of brief cerebral ischemia/reperfusion and dehydroepoandrosterone treatment on components of NMDA receptor-mediated signalling in rat hippocampus and prefrontal cortex

dc.contributor.advisorMartinović, Jelena
dc.contributor.otherNedeljković, Nadežda
dc.contributor.otherDrakulić, Dunja
dc.creatorZarić, Marina M.
dc.date.accessioned2020-03-09T09:12:35Z
dc.date.available2020-03-09T09:12:35Z
dc.date.available2020-07-03T08:15:05Z
dc.date.issued2019-12-04
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=7338
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/12179
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:21574/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025242546
dc.description.abstractStanje moţdane ishemije/reperfuzije (I/R) karakteristično je za cerebrovaskularna oboljenja kao što su moţdani udar i tranzitorni ishemijski atak (TIA). Promena signalizacije posredovana N-metil-D-aspartat (NMDA) receptorom ima značajnu ulogu u I/R-uzrokovanom oštećenju, dok je dehidroepiandrosteron (DHEA), pozitvni alosterični modulator NMDA receptora, najčešće okarakterisan kao neuroprotektivan u tretmanu ishemičnih stanja. U ovoj disertaciji ispitivana je proteinska ekspresija komponenti kompleksa NMDA receptora i njegove nishodne signalizacije u hipokampusu i prečeonoj kori muţjaka pacova Wistar soja 24 sata nakon podvezivanja obe zajedničke karotidne arterije u trajanju od 15 min i/ili efekat tretmana DHEA primenjenog 4 sata od hirurške procedure. Praćenje senzo-motorne funkcije i prisustvo infarktnih lezija na presecima celog mozga korišćeno je za validaciju I/R modela za proučavanje blaţih ishemičnih stanja poput TIA. Takođe, izvršeno je ispitivanje efekata I/R i tretmana na histo/morfološkom nivou. Odsustvo senzo-motornih deficita i infarktnih lezija kao i očuvana struktura tkiva i morfologija neurona u hipokampusu i prečeonoj kori nakon I/R ukazuju na potencijalnu primenu modela u ispitivanju umerenih ishemičnih stanja. Region-specifične promene signalnog puta NMDA receptor/neuralna azot oksid sintaza/azot oksid nakon kratkotrajne I/R govore u prilog većoj osetljivosti hipokampusa u odnosu na prečeonu koru. Efekat DHEA uočen je isključivo nakon I/R, vraćajući u prečeonoj kori parametare na kontrolnu vrednost, dok u hipokampusu promene Bax/Bcl -2 odnosa i potencijala mitohondrijske membrane ukazuju na pokretanje pro-apoptotskih dešavanja. Stoga, prethodno okarakterisani neuroprotektivni efekat DHEA treba dodatno istraţiti.sr
dc.description.abstractCerebral ischemia/reperfusion (I/R) is characteristic of cerebro-vascular diseases such as stroke and transient ischemic attack (TIA). Alterations of Nmethyl- D-aspartate (NMDA) receptor-mediated signalling pathway are well recognized features of I/R-governed damage, while dehydroepiandrosterone (DHEA), its positive allosteric modulator, has been previously described as neuroprotective and potentially promising for therapy of ischemic conditions. In this doctoral dissertation changes of components of the NMDA receptor complex and downstream signalling in hippocampus and prefrontal cortex were examined in male Wistar rats 24 h following 15 min bilateral common carotid artery occlusion. In addition, effects of 4 h post-surgical DHEA treatment were investigated. Sensory-motor function and presence of infarct lesions were used to validate suitability of I/R model for studying mild ischemic conditions such as TIA. Additionally, effects of I/R and treatment were evaluated on histo/morphological level. Absence of sensory-motor deficits and infarct lesions, as well as preserved tissue structure and overall neuronal morphology in hippocampus and prefrontal cortex following I/R and treatment were detected indicating suitability of used I/R model for investigation of mild ischemic states. Regionspecific postischemic changes of NMDA receptor/neuronal nitric oxide synthase/nitric oxide following short-term I/R indicate higher sensitivity of hippocampus compared to prefrontal cortex. DHEA effect was detected exclusively following I/R, returning the parameters in prefrontal cortex to the control value, while hippocampal Bax/Bcl-2 ratio and mitochondrial membrane potential changes indicate the initiation of pro-apoptotic events. Therefore, previously reported neuroprotective effect of DHEA should be considered with caution and further investigated.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173044/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectmoţdana ishemija/reperfuzija, blaga ishemična stanja, tranzitorni ishemijski atak, dehidroepiandrosteron, NMDA receptor, hipokampus, prečeona kora, pacovsr
dc.subjectcerebral ischemia/reperfusion, mild ischemic conditions, transient ischemic attack, dehydroepiandrosterone, NMDA receptor, hippocampus, prefrontal cortex, raten
dc.titleEfekat kratkotrajne moždane ishemije/reperfuzije i tretmana dehidroepiandrosteronom na komponente signalnog puta NMDA receptora u hipokampusu i prečeonoj kori pacovasr
dc.title.alternativeEffects of brief cerebral ischemia/reperfusion and dehydroepoandrosterone treatment on components of NMDA receptor-mediated signalling in rat hippocampus and prefrontal cortexen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3525/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3526/IzvestajKomisije22300.pdf


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