Morphological, biochemical and behavioral changes in medial prefrontal and orbital frontal cortex of rat induced by maternal deprivation

[J. Poleksić]

102 str.

Medicina - Neuronauke / Medicine - Neuroscience

raumatska iskustva proživljena tokom ranog životnog doba povećavaju mogućnost razvoja psihičkih oboljenja 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 visokom osetljivošću na stres, Wistar pacove 9 dana starosti podvrgli smo 24 – časovnoj maternalnoj deprivaciji (MD). Kod mladih adultnih mužjaka pacova, detaljna anatomska imunohistohemijska analiza subregiona PFC - a je pokazala smanjenje GAD67 i CCK imunopozitivnih ćelija u površinskim slojevima medijalne orbitalne kore (MO) dok je u rostralnom delu ventrolateralne orbitalne kore (roVLO) smanjena gustina GAD67 imunopozitivnih ćelija bila prisutna u celokupnoj debljini kore. Površinski slojevi rostralnog dela cingularne kore (roCg1) i duboki slojevi prelimbičke kore (PrL) takođe su bili pogođeni ranim odvajanjem mladunaca od majke, pri čemu je u ovim subregionima MD uzrokovala smanjenje gustine PV imunopozitivnih ćelija. Strukturne promene GABAergičkog sistema bile su praćene ushodnom regulacijom BDNF – a, uz odsustvo opšte mikroglijalne aktivacije kako u neoenatalnom tako i u mladom adultnom dobu, kako je utvrđeno metodom Western blot. Kada je kod mladih adultnih MD životinja ispitana kognitivna fleksibilnost u T – lavirintu, pronađeno je suptilno oštećenje reverznog učenja što ukazuje na blago oštećenje funkcije PFC – a. Sveukupno, rezultati sprovedenog istraživanja pokazuju da MD uzrokuje subregion zavisno smanjenje gustine interneurona, praćeno povećanjem sinaptičke plastičnosti i disfunkcijom PFC – a. Takođe, dobijeni rezultati ističu kompleksnu prirodu uticaja RTI na razvoj interneurona, ali i značaj očuvanosti GABAergičkog sistema u kognitivnom funkcionisanju.

Stressful events experienced during early life are associated with increased vulnerability of developing psychopathology in adulthood. In the present study, we exposed 9 – day - old Wistar rats to 24 hour maternal deprivation (MD) with the aim to investigate the impact of early life stress (ELS) on morphological, biochemical and functional aspects of the prefrontal cortex (PFC), a brain region particularly sensitive to stress. We found that in superficial medial orbital cortex (MO), young adult male rats had reduced density of GAD67 and CCK immunopositive cells while the rostral part of ventral lateral orbital cortex (roVLO) showed a decrease in the density of GAD67 immunopositive cells in both superficial 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 PV immunopositive cellular density. Furthermore, MD induced an upregulation of BDNF, while it did not affect 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, MD rats showed a subtle impairment in reversal learning indicating a mildly affected PFC function. Taken together, our results demonstrate that MD reduces the density of interneurons in particular PFC areas at young adulthood and may alter synaptic plasticity accompanied by PFC dysfunction. These findings point out the complex effect of ELS on interneuron development as well as the importance of preserved GABAergic system on cognitive functioning.

maternalna deprivacija, prefrontalna kora, interneuroni, parvalbumin, holecistokinin, sinaptička plastičnost, BDNF, mikroglija, kognitivna fleksibilnost

maternal deprivation, prefrontal cortex, interneurons, parvalbumin, cholecystokinin, synaptic plasticity, BDNF, microglia, cognitive flexibility

616.8-092.9:611.8(043.3)

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