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    <ns1:title language="sr">Morfološke, biohemijske i bihejvioralne promene u medijalnom prefrontalnom i orbitofrontalnom korteksu mozga pacova uslovljene maternalnom deprivacijom</ns1:title>
    <ns2:subtitle language="sr">doktorska disertacija</ns2:subtitle>
    <ns2:alt_title language="sr">Morphological, biochemical and behavioral changes in medial prefrontal and orbital frontal cortex of rat induced by maternal deprivation : doctoral dissertation</ns2:alt_title>
    <ns1:language>sr</ns1:language>
    <ns1:description language="sr">raumatska iskustva proživljena tokom ranog životnog doba povećavaju mogućnost razvoja psihičkihoboljenja kasnije tokom života. Kako bi ispitali uticaj ranog traumatskog iskustva (RTI) na morfološke,biohemijske i funkcionalne osobine prefrontalne kore (PFC), moždanog regiona koji se odlikuje visokomosetljivošću na stres, Wistar pacove 9 dana starosti podvrgli smo 24 – časovnoj maternalnoj deprivaciji(MD). Kod mladih adultnih mužjaka pacova, detaljna anatomska imunohistohemijska analiza subregionaPFC - a je pokazala smanjenje GAD67 i CCK imunopozitivnih ćelija u površinskim slojevima medijalneorbitalne kore (MO) dok je u rostralnom delu ventrolateralne orbitalne kore (roVLO) smanjena gustinaGAD67 imunopozitivnih ćelija bila prisutna u celokupnoj debljini kore. Površinski slojevi rostralnogdela cingularne kore (roCg1) i duboki slojevi prelimbičke kore (PrL) takođe su bili pogođeni ranimodvajanjem mladunaca od majke, pri čemu je u ovim subregionima MD uzrokovala smanjenje gustinePV imunopozitivnih ćelija. Strukturne promene GABAergičkog sistema bile su praćene ushodnomregulacijom BDNF – a, uz odsustvo opšte mikroglijalne aktivacije kako u neoenatalnom tako i u mladomadultnom dobu, kako je utvrđeno metodom Western blot. Kada je kod mladih adultnih MD životinjaispitana kognitivna fleksibilnost u T – lavirintu, pronađeno je suptilno oštećenje reverznog učenja štoukazuje na blago oštećenje funkcije PFC – a. Sveukupno, rezultati sprovedenog istraživanja pokazuju daMD uzrokuje subregion zavisno smanjenje gustine interneurona, praćeno povećanjem sinaptičkeplastičnosti i disfunkcijom PFC – a. Takođe, dobijeni rezultati ističu kompleksnu prirodu uticaja RTI narazvoj interneurona, ali i značaj očuvanosti GABAergičkog sistema u kognitivnom funkcionisanju.</ns1:description>
    <ns1:description language="en">Stressful events experienced during early life are associated with increased vulnerability of developingpsychopathology in adulthood. In the present study, we exposed 9 – day - old Wistar rats to 24 hourmaternal deprivation (MD) with the aim to investigate the impact of early life stress (ELS) onmorphological, biochemical and functional aspects of the prefrontal cortex (PFC), a brain regionparticularly sensitive to stress. We found that in superficial medial orbital cortex (MO), young adult malerats had reduced density of GAD67 and CCK immunopositive cells while the rostral part of ventral lateralorbital cortex (roVLO) showed a decrease in the density of GAD67 immunopositive cells in bothsuperficial and deep layers. In addition, superficial rostral part of area 1 of the cingulate cortex (roCg1)and deep prelimbic cortex (PrL) were also affected by MD indicated by the reduction in PVimmunopositive cellular density. Furthermore, MD induced an upregulation of BDNF, while it did notaffect the overall expression of Iba1 in neonatal or young adult PFC as measured by Western blot.Interestingly, when young adult male rats were subjected to a behavioral flexibility test in a T-maze, MDrats showed a subtle impairment in reversal learning indicating a mildly affected PFC function. Takentogether, our results demonstrate that MD reduces the density of interneurons in particular PFC areas atyoung adulthood and may alter synaptic plasticity accompanied by PFC dysfunction. These findingspoint out the complex effect of ELS on interneuron development as well as the importance of preservedGABAergic system on cognitive functioning.</ns1:description>
    <ns1:description language="sr">Medicina - Neuronauke / Medicine - Neuroscience  Datum odbrane: 28.09.2022. </ns1:description>
    <ns1:keyword language="sr">maternalna deprivacija, prefrontalna kora, interneuroni, parvalbumin, holecistokinin, sinaptička plastičnost, BDNF, mikroglija, kognitivna fleksibilnost</ns1:keyword>
    <ns1:keyword language="en">maternal deprivation, prefrontal cortex, interneurons, parvalbumin, cholecystokinin, synaptic plasticity, BDNF, microglia, cognitive flexibility</ns1:keyword>
    <ns1:keyword language="sr">616.8-092.9:611.8(043.3) </ns1:keyword>
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        <ns3:firstname> Joko, 1989-</ns3:firstname>
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        <ns3:firstname> Branka, 1981-</ns3:firstname>
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        <ns3:firstname> Dubravka, 1985-</ns3:firstname>
        <ns3:lastname>Aleksić</ns3:lastname>
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      <ns1:ext_role>član komisije</ns1:ext_role>
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        <ns3:firstname> Tatjana, 1981-</ns3:firstname>
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    <ns7:keyword language="sr" seq="0">maternalna deprivacija, prefrontalna kora, interneuroni, parvalbumin, holecistokinin,sinaptička plastičnost, BDNF, mikroglija, kognitivna fleksibilnost</ns7:keyword>
    <ns7:keyword language="sr" seq="1">maternal deprivation, prefrontal cortex, interneurons, parvalbumin, cholecystokinin,synaptic plasticity, BDNF, microglia, cognitive flexibility</ns7:keyword>
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