”Expresión of dopaminergic transcription factors in prenatally stress rats at different ages”.

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

Congreso; XXXiX Annual Soceity for Neuroscience; 2009

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 dopamine (DA) D2-type receptor (D2R) levels in prefrontal cortex (PFc), nucleus accumbens (NAc) core and hippocampus (Hip) and a decrease of amphetamine stimulated DA levels in NAc shell and PFc. It has recently been identified two transcription factors (TFs), Nurr1 and Pitx3 which are expressed at critical moments of DA neurons differentiation. Employing an immunocytochemistry approach, we studied the expression levels of these TFs and of TH, the rate limiting step enzyme in the synthesis of DA, in mesencephalon slices of prenatally stressed rats at different ages. We found a ubiquitous distribution of Nurr1 whereas Pitx3 remains restricted to 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. 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. Since dopamine release is still impaired at adult ages we speculate that other steps in the dopamine synthesis and storage metabolism is impaired such as dopamine transporters VMAT2 or DAT. The area selectivity of the increase of the TFs towards VTA and the mesolimbic pathway indicates that an insult received during the prenatal period will exert mainly motivational, emotional and reward behaviour impairments in the adult life.