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The effect of propofol induced anesthesia on synaptic plasticity, dopaminergic system activity and behaviour of juvenile rats

dc.contributor.advisorPešić, Vesna
dc.contributor.otherDacić, Sanja
dc.contributor.otherKanazir, Selma
dc.contributor.otherPešić, Vesna
dc.creatorPavković, Željko Z.
dc.date.accessioned2018-12-15T09:37:18Z
dc.date.available2018-12-15T09:37:18Z
dc.date.available2020-07-03T08:07:27Z
dc.date.issued2018-09-21
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/10343
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6327
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:18997/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1025197746
dc.description.abstractPropofol je često korišćeni anestetik u modernoj medicini. Adiktivni potencijal propofola je uočen, kao i uticaj na memorijski proces. Međutim, oba fenomena su još uvek nedovoljno istražena. Imajući u vidu da je adolescencija period izuzetne osetljivosti na dejstvo adiktivnih supstanci i intenzivne maturacije mnemoničkog potencijala, cilj ovog rada je bio da se ispita uticaj jednokratnog izlaganja propofolskoj anesteziji, što je tipičan način kliničke primene anestetika, na dopaminsku signalizaciju, sinaptičku i neuronsku aktivnost u različitim regionima mozga i ponašanje juvenilnih/peripubertetskih pacova, kao model sistema humanog periadolescentnog razvoja. Efekti su analizirani 4, 24 i 48 sati nakon tretamana, kod mužjaka Wistar pacova starih 35 dana. Dobijeni rezultati su po prvi put ukazali da izlaganje propofolskoj anesteziji izaziva promene u ekspresiji/fosforilaciji signalnih molekula koji su već prepoznati kao značajni za dejstvo adiktivnih supstanci. Od svih analiziranih dopaminoceptivnih moždanih regiona (medijalni prefrontalni korteks, strijatum i talamus) jedino su u talamusu uočene značajne promene u ekspresiji fosforilisane/aktivirane forme DARPP-32 proteina, pokazatelja postsinaptičke dopaminske signalizacije, 4 i 24 sata nakon tretmana, i bile su praćene povećanom ekspresijom FosB/ΔFosB proteina, biohemijskog pokazatelja neuronske aktivnosti. Promene su lokalizovane u paraventrikularnom talamičkom jedru i mediodorzalnom talamusu. U strijatumu i medijalnom prefrontalnom korteksu je uočen porast u ekspresiji fosforilisane forme CaMKIIα, biohemijskog senzora sinaptičke aktivnosti koji ima važnu ulogu u pamćenju prethodnog izlaganja adiktivnim supstancama. Smanjenje u intenzitetu anksioznosti (procenjeno na osnovu rezultata dobijenih u testu svetlo/tamne kutije i uzdignutog krstastog lavirinta) je zabeleženo 24 sata nakon tretmana, kada je uočen i pad u ekspresiji FosB proteina u strijatumu, što se može tumačiti kao traženje senzacija usled smanjene aktivnosti moždanog regiona značajnog za osećaj zadovoljstva i motivisanost. Pojačan motorički odgovor na d-amfetamin i fenciklidin je uočen 24 sata nakon tretmana (ukrštena senzitizacija), kao potvrda da bez obzira na različite primarne mehanizme dejstva propofol i dve korišćene droge koriste iste neuronske puteve za ostvarivanje psihomotoričkih efekata...sr
dc.description.abstractPropofol is a commonly used anesthetic in modern medicine. Addictive potential of propofol is observed, as well as the impact on the memory process. However, both phenomena are still insufficiently explored. Bearing in mind that adolescence is a period of extreme sensitivity to addictive substances and intense maturation of the mnemonic potential, the aim of this study was to examine the effect of a single exposure to propofol anesthesia, which is a typical method of its clinical application, on dopaminergic signaling, synaptic and neuronal activity in different brain regions and behavior of juvenile/peripubertal rats, as a model system of human periadolescencent development. The effects were analyzed 4, 24 and 48 hours after the treatment, in male Wistar rats aged 35 days. The obtained findings for the first time showed that exposure to propofol anesthesia caused changes in the expression/phosphorylation of signal molecules that are already recognized as significant for the action of the addictive substances. Of all the analyzed dopaminoceptive brain regions (medial prefrontal cortex, striatum and thalamus), significant changes in the expression of the phosphorylated/activated form of DARPP-32 protein, indicator of postsynaptic dopaminergic signalling, were observed only in the thalamus, 4 and 24 hours after the treatment, and were accompanied by increased expression of FosB/ΔFosB protein, a biochemical indicator of neuronal activity. The alterations were localized in the paraventricular thalamic nucleus and the mid-dorsal thalamus. An increase in the expression of the phosphorylated form of CaMKIIα, a biochemical sensor of synaptic activity that has an important role in memory on addictive substances exposure, was detected in striatum and medial prefrontal cortex. Reduction in the intensity of anxiety (estimated in accordence to the data obtained in the light/dark box and elevated plus maze tests) was observed 24 hours after the treatment, along with the decrease in the expression of FosB protein in striatum, which can be interpreted as a sensation seeking due to decreased activity of brain region important for a pleasure/motivation...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173051/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173056/RS//
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectpropofolsr
dc.subjectpropofolen
dc.subjectperipubertetsr
dc.subjectzavisnost/adikcijasr
dc.subjectanksioznostsr
dc.subjectdopaminsr
dc.subjectsinaptička aktivnostsr
dc.subjectsinaptička stabilnostsr
dc.subjectprostorna habituacijasr
dc.subjectprepoznavanje novog objektasr
dc.subjectepizodična memorijasr
dc.subjectperipubertyen
dc.subjectaddicationen
dc.subjectanxietyen
dc.subjectdopamineen
dc.subjectsynaptic activityen
dc.subjectsynaptic stabilityen
dc.subjectspatial habituationen
dc.subjectnovel object recognitionen
dc.subjectepisodic memoryen
dc.titleEfekti anestezije indukovane propofolom na sinaptičku plastičnost, aktivnost dopaminskog sistema i ponašanje juvenilnih pacovasr
dc.title.alternativeThe effect of propofol induced anesthesia on synaptic plasticity, dopaminergic system activity and behaviour of juvenile ratsen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-SA
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/1603/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1604/IzvestajKomisije18505.pdf
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/1604/IzvestajKomisije18505.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/1603/Disertacija.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_10343


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