EXPRESSION OF DOPAMINERGIC TRANSCRIPTION FACTORS IN PRENATALLY STRESS RATS AT DIFFERENT AGES

KATUNAR M.R.; ADROVER E; SAEZ T.; BRUSCO A.; ANTONELLI M.C

CHICAGO

Congreso; XXXIX Reunión Anual de la Society for Neuroscience; 2009

SFN

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. We have previously shown that prenatal stress (PS) increases D2-type dopamine (DA) receptor (D2R) levels in frontal cortex, nucleus accumbens (NAcc) core and hippocampus. We also observed a decrease of amphetamine stimulated dialysate in prefrontal cortex of prenatally stressed rats at postnatal day 60 (PND 60) compared with controls. After amphetamine or nicotine stimulation, DA levels were higher at PND 60 in NAcc shell. 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 throughout adult life. In addition, we measured the expression levels of Tyrosine hydroxilase (TH), which is the rate limiting enzyme in the synthesis of DA. Employing an inmunocitochemistry approach, we studied the expression levels of these factors and TH in mesencephalon slices of prenatally stressed rats at different ages. We found a ubiquitous distribution of Nurr1 in cerebral cortex, hippocampus, thalamus, amygdala and midbrain whereas Pitx3 remains restricted to the mesencephalic DA system such as substancia nigra (SN) and ventral tegmental area (VTA). Our results show that the expression of both Nurr1 and Pitx3 increased in prenatally stressed offspring in the VTA area at PND 7 and PND 60, whereas no changes were observed in SN areas. TH expression was reduced at PND 7 in VTA and recovered to control values at PND 28 and 60. Taken together these results show that several components of the limbic dopaminergic system are disregulated as a consequence of the prenatal insult. The increase of the specific dopaminergic transcription factors and TH expression might be a compensatory mechanism to counteract the reduction in dopamine levels observed in PFC, which in turn might be upregulating D2 dopaminergic receptors.