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Morphological and biochemical changes in the prefrontal cortex, amygdala and hippocampus of the rat brain conditioned by single prolonged stress

dc.contributor.advisorPetronijević, Nataša
dc.contributor.otherPuškaš, Laslo
dc.contributor.otherIvković, Maja
dc.contributor.otherAksić, Milan
dc.contributor.otherStojšić-Džunja, Ljubica
dc.creatorPetrović, Romana Lj.
dc.date.accessioned2019-02-08T15:49:36Z
dc.date.available2019-02-08T15:49:36Z
dc.date.issued2018-09-25
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6595
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:19388/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50780943
dc.identifier.urihttp://nardus.mpn.gov.rs/123456789/10742
dc.description.abstractPosttraumatski stresni poremećaj (PTSP) je veoma rasprostranjeno i onesposobljavajuće oboljenje. Uprkos raspoloživoj psihofarmakološkoj i na dokazima zasnovanoj kognitivno-bihejvioralnoj terapiji, kod značajnog broja PTSP pacijenata nema odgovora na konvencionalnu terapiju, što pokazuje da su patogenetski mehanizmi u PTSP-u još uvek nedovoljno ispitani. Pojedinačni produženi stres (PPS) predstavlja koristan animalni model PTSP-a za razumevanje patofiziologije oboljenja i razvoj novih terapijskih strategija. Preovlađujući neuroanatomski model PTSP-a, naglašava centralni značaj amigdale kao i njene interakcije sa medijalnim prefrontalnim korteksom i hipokampusom. Mnoge studije pokazuju da su neuropatološke i psihološke alteracije kod PTSD pacijenata povezane sa oksidativnim stresom u mozgu. Glavni izvori slobodnih radikala u ćeliji su mitohondrijalni respiratorni lanac i sistem nikotinin adenin dinukleotid fosfat (NADPH) fosfataze. Ekscitatorno/inhibitorni disbalans zbog disfunkcionalne GABA-ergičke neuronske mreže, ima patofiziološki značaj u mnogim psihijatrijskim oboljenjima. Parvalbumin inhibitorni interneuroni su veoma značajni za održavanje odgovarajuće ekscitatorno/inhibitorne ravnoteže i u sinhronizaciji visokofrekventnog neuronskog pražnjenja i mogu biti uključeni u patološko učenje straha u PTSP-u. Takođe, mnoge studije su pokazale učešće različitih neuropeptida u procesiranju stresnih stimulusa i stresnom odgovoru. Cilj: Cilj ove disertacije se sastojao u ispitivanju uticaja pojedinačnog produženog stresa na: (1) parametre oksidativnog stresa uključujući nivo malondialdehida (MDA), sadržaj redukovanog glutationa (GSH), aktivnost glutation peroksidaze (GPx), superoksid dizmutaze (SOD) i katalaze (CAT), i ekspresiju SOD1 i SOD2; (2) moguće generatore slobodnih radikala: mitohondrijalni respiratorni lanac, određivanjem aktivnosti kompleksa I i citohrom c oksidaze (COX) i NADPH oksidazu, određivanjem ekspresije membranskih (gp91phox i p22phox) i citosolnih (p67phox) subjedinica ovog enzima i (3) ukupan broj neurona (NeuN pozitivne ćelije), broj parvalbumin (PV) i kalbindin (CB) pozitivnih GABA-ergičkih neurona i broj supstanca P (SP), enkefalin (ENK) i galanin (GAL) pozitivnih peptidergičkih neurona u prefrontalnom korteksu (PFK), hipokampusu i amigdali mozga pacova...sr
dc.description.abstractPost-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Despite the availability of pharmacological and evidence-based cognitive behavioral therapy, a considerable number of PTSD patients do not respond to the conventional therapy indicating that pathogenetic mechanisams of PTSD are currently not sufficiently explored. Single prolonged stress (SPS) is useful animal model of PTSD for understanding the pathophysiology of the disorder and the development of new treatments. A prevailing neurocircuitry model of PTSD emphasizes the role of the amygdala, as well as its interactions with the medial prefrontal cortex (mPFC) and hippocampus. Increasing evidence indicates that neuropathological and psychological alterations in PTSD sufferers are related to brain oxidative stress. The major sources of reactive oxygen species (ROS) in cells are mitochondrial respiratory chain and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Excitatory-inhibitory disbalance through disfunctional GABA-ergic circuits is implicated in many psychiatric disorders. Parvalbumin inhibitory interneurons are very important for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization and could be implicated in pathological fear learning in PTSD. Also, many studies have shown the participation of different neuropeptides in the processing of stressful stimuli and the stress response. Aim: The aims of present dissertation were to elucidate the effects of single prolonged stress on: (1) oxidative stress parameters, including malondialdehyde (MDA) level, reduced glutathione (GSH) level, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity and expression of SOD1 and SOD2(2) possible sources of free radicals: mitochondrial respiratory chain by determining of Complex I and cytochrome c oxidase (COX) activity and NADPH oxidase by determining of the expression of membrane (gp91phox, p22phox) and cytosolic (p67phox) subunits of this enzyme; (3) total number of neurons (NeuN positive cells), number of parvalbumin (PV) and calbindin (CB) positive GABA-ergic neurons and number of substance P(SP), enkephaline (ENK) and galanine (GAL) positive peptidergic neurons in the rat prefrontal cortex, hippocampus and amygdala.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175058/RS//
dc.rightsAutorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
dc.sourceУниверзитет у Београдуsr
dc.subjectpojedinačni produženi stres, posttraumatski stresni poremećaj, amigdala, NADPH oksidaza, supstanca P, galanin, enkefalinsr
dc.subjectsingle prolonged stress, post-traumatic stress, amygdala, NADPH oxidase, substance P, galanin, enkephalineen
dc.titleMorfološke i biohemijske promene u prefrontalnom korteksu, amigdaloidnom telu i hipokampalnoj formaciji mozga pacova uslovljene pojedinačnim produženim stresomsr
dc.title.alternativeMorphological and biochemical changes in the prefrontal cortex, amygdala and hippocampus of the rat brain conditioned by single prolonged stressen
dc.typePhD thesis


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