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

KATUNAR MR, ADROVERR E, SAEZ T, BRUSCO A, ANTONELLI M

Chicago USA

Congreso; SFN MEETING; 2009

Society for Neuroscience

Rats exposed to different types do stress during the last week of pregnancy produce offspring that show severe aormalities in neural development and brain morphology that persist into adulthood particularly in dopaminergic neurotransmission. We have previously shon that prernatal stres (PS) increases dopamine (DA) D2-type receptor (D2R) levels in prefrontal corrtex (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) Nurrs and Pitx3 which are expressed at critical moments of DA neurons differentiation. Employing and immuncytochemistry approach, we studied the expression levels of these TFs and TH, the rate limiting step enzime in the synthesis of DA, in mesencephalon slices of prenatally stressed rrats at different ages. We found a ubiquitous distribution of Nurr1 whereas Pitx3 remains restricted to substantia nigra (SN) and ventral tegmental area (VTA). Our results show that the expression of both Nurr1 and Pitx3 are modified in prenatally stressed offspring in the VTA area at PND7,28 and60, whereas no changes were observed in SN areas. TH expression was reduced at PND7 in VTA and recovered ot control values at PND28 and 60. The increase of the specific dopaminergic transcrription factors and TH expression might be a compensatory mechanism to counteract the reduction in DA levels observed in PFC, which in turn might be upregulating D2R. Since DA release is still decreased at adult ages we speculate that other steps in the dopamine synthesis and storage metabolism might be 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 perido will exert mainly motivational, emotional and reward behaviour impairments in the adult life.