Naslov (srp)

Efekat estradiola u modulaciji apoptotskih signala u moždanoj kori i hipokampusu pacova tokom hronične moždane hipoperfuzije : doktorska disertacija

Autor

Stanojlović, Miloš R.

Doprinosi

Drakulić, Dunja
Nedeljković, Nadežda, 1967-
Horvat, Anica, 1952-
Stojiljković, Mirjana, 1947-
Grković, Ivana

Opis (srp)

Iako se ishemijske bolesti mozga, koje se karakterišu pogoršanjem motornih i kognitivnih funkcija, uključujući smanjenje sposobnosti učenja i memorije, intenzivno proučavaju poslednjih 20 godina malo je poznato o molekulskim mehanizmima njihovog nastanka, kao i odgovarajućim terapijama. Osnovni cilj ove doktorske disertacije je bio da se ispita efekat hroničnog tretmana polnim hormonom, estradiolom, na apoptotske puteve u kortikalnim i hipokampalnim ćelijama polno zrelih mužjaka pacova Wistar soja u stanju nametnute hronične moždane hipoperfuzije. Tome je predhodilo proučavanje efekta moždane hipoperfuzije na složenu kaskadu apoptotskih signalnih puteva u kori prednjeg mozga i hipokampusu pacova u različitim vremenskim tačkama. Za potrebe prvog dela eksperimenta jedna grupa pacova je lažno operisana, dok je druga grupa podvrgnuta operaciji trajnog podvezivanja zajedničkih karotidnih arterija. Jedinke obe grupe su ostavljene na preživljavanju 3, 7 ili 90 dana. Za potrebe drugog dela eksperimenta pacovi su podeljeni u dve grupe: životinje kojima su trajno podvezane zajedničke karotidne arterije, tretirane 7 dana lanenim uljem i jedinke podvrgnute operaciji trajnog podvezivanja zajedničkih karotidnih arterija i tretirane 7 dana estradiolom (33.3 g/kg/dan, rastvoren u lanenom ulju). Praćeni su sledeći parametri: obim neuralne smrti, fragmentacija DNK koja je karakteristična za apoptozu, kao i promene u ekspresiji proteina i iRNK markera procesa ćelijske smrti odnosno preživljavanja ćelija. Rezultati ove doktorske disertacije pokazuju da se u zadatim eksperimentalnim uslovima, u kori prednjeg mozga u ranim vremenskim tačkama javljaju neurodegenerativne promene koje prate ekspresiju apoptotskih molekula u neprečišćenoj membranskoj frakciji, dok se u kasnije aktiviraju adaptivni i kompenzatorni mehanizmi. U hipokampusu je uočen specifičan vremenski-zavisan trend ekspresije analiziranih pro- i anti-apoptotskih molekula koji dovode do pojave odložene ćelijske smrti. Na osnovu proučavanja efekata hroničnog tretmana malim dozama estradiola u stanju nametnute moždane hipoperfuzije može se zaključiti da ovaj potentni polni hormon ima kapacitet da oblikuje odgovor ispitivanih moždanih struktura...

Opis (srp)

Biologija - Neurobiologija / Biology- Neurobiology Datum odbrane: 06.06.201

Opis (eng)

Although ischemic brain diseases, characterized by decline of motor and cognitive functions, including reducing the ability of learning and memory, have been intensively studied over the past 20 years, the molecular mechanisms of their generation, as well as appropriate treatments are still matter of controversy. The main goal of this PhD thesis was to investigate the effects of repeated estradiol treatment on apoptotic pathways in cortical and hippocampal cells of adult male Wistar rats in a state of imposed chronic cerebral hypoperfusion. This was preceded by the study of the effects of cerebral hypoperfusion on complex cascade of apoptotic signalling pathways in the cerebral cortex and hippocampus of rats at different time points. For the purposes of the first part of the experiment, one group of rats was sham operated, while the other group was subjected to permanent ligation of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. For the second part of the experiment, the rats were divided into two groups: animals that underwent permanent common carotid artery occlusion, treated for 7 days with linseed oil and rats subjected to permanent ligation of the common carotid arteries, treated for 7 days with estradiol (33.3 μg/kg/day, dissolved in linseed oil). Parameters that were monitored are: volume of neuronal death, DNA fragmentation typical for apoptosis, as well as changes in mRNA and protein expressions of cell death or survival markers. The results obtained in this dissertation indicate that in cerebral cortex at two early investigated time points, the expression of apoptotic molecules in synaptosomal fraction is accompanied with neurodegenerative changes, while later adaptive and compensatory mechanisms are activated. In hippocampus, a specific time-dependent expression of analyzed pro- and anti-apoptotic molecules is associated with delayed apoptotic death. Furthermore, according to gained data, repeated estradiol treatment in state of imposed chronic cerebral hypoperfusion exerts a potent capacity to profile the response of investigated brain structures, through modulation of expression of mitochondrial apoptotic pathway markers. Also, results for synaptosomal, cytosolic, mitochondrial and nucleus fractions of both investigated brain structures, point that protective effects of estradiol are either less pronounced in synaptosomal fraction or ischemic changes in this cell fraction are significant, thus applied treatment is not sufficient to compensate the effects of the injury...

Jezik

srpski

Datum

2014

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 2.0 AT - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 2.0 Austria License.

http://creativecommons.org/licenses/by-nc-nd/2.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Molekularna neurobiologija

moždana hipoperfuzija, estradiol, mozak, apoptoza/preživljavanje, pacov

577.175.6:616.8-005.4(043.3)

OSNO - Opšta sistematizacija naučnih oblasti, Molekularna neurobiologija

cerebral hypoperfusion, estradiol, brain, apoptosis/survival, rat