Expression of dopaminergic transcription factors and mesencephalic connectivity in prenatally stressed adults rats

MR. KATUNAR, E ADROVER, P. MORALES, A BRUSCO, M. HERRERA-MARSCHITZ Y M.C. ANTONELLI.

Buzios, Brasil.

Congreso; I Congreso IBRO/LARC de Neurociencias de América Latina, Caribe y Península Ibérica; 2008

Rats exposed to different types of stress during the last week of pregnancy produce offspring that show severe anomalies in neural development and brain morphology that persist into adulthood particularly in dopaminergic neurotransmission. It has recently been identified two transcription factors (TFs), Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation. Their genetic expression is activated immediately after these neurons determination and maintained through adult life. Employing an inmunocitochemistry approach, we studied the expression levels of these factors in mesencephalon slices of prenatally stressed adult rats. In addition, we evaluated the prenatal stress (PS) effects over the growth of a triple organotypic cultures of substantia nigra (SN), caudate putamen (Cpu) and frontal cortex (FC). The cultures of PS rats showed less growth when it is compared with the control group, showing that the PS could be affecting the normal connectivity of the corticonigrostratial system. Nurr1 expression was localized in compact and reticular Sustantia Nigra, (SNc and SNr), ventral tegmental area (VTA) and cortex regions, whereas Pitx3 expression was restricted to SNc, SNr and to VTA. Cuantifications of Nurr1 and Pitx3 expression showed that both TFs increased in prenatally stressed adult offspring in the VTA area, whereas no changes were observed in SN areas. Since both TFs modulates the expression of tirosine hidroxylase, the key enzyme in dopamine synthesis, the increase of TFs in the adult prenatally stressed rat might be a compensatory mechanism to counteract the decrease of dopamine levels observed previously.