Expression of dopaminergic transcription factors in prenatally stress rats at different ages

MR KATUNAR, E ADROVER , T. SAEZ, A BRUSCO Y MC. ANTONELLI.

Chicago, Ill. USA.

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

st1:*{behavior:url(#ieooui) } <!-- /* Font Definitions */ @font-face {font-family:"Comic Sans MS"; panose-1:3 15 7 2 3 3 2 2 2 4; mso-font-charset:0; mso-generic-font-family:script; mso-font-pitch:variable; mso-font-signature:647 0 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES; mso-fareast-language:ES;} p.MsoBodyText2, li.MsoBodyText2, div.MsoBodyText2 {margin:0cm; margin-bottom:.0001pt; text-align:justify; mso-pagination:widow-orphan; font-size:10.0pt; mso-bidi-font-size:12.0pt; font-family:"Comic Sans MS"; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:EN-US; mso-fareast-language:ES;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> M. R. Katunar1, E. Adrover1, , T. Saez2, , A. Brusco2, and M. C. Antonelli1. 1IQUIFIB (UBA-CONICET), Facultad de Farmacia y Bioquímica. UBA. 2IBCN. Facultad de Medicina.UBA. Buenos Aires. ARGENTINA.     Stress applied to the gestant dam was shown to produce long-term effects on the adult offspring. 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 found that two of the key regulators for the development of dopaminergic neurons are Nurr1 and Pitx3, which are crucial for the expression of a set of genes involved in DA metabolism and there is a growing evidence to suggest that these pathways are interconnected at functional level. Employing an immunocytochemistry approach, we studied the expression levels of these transcription levels 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 SN and recovered to control values at PND 28 and 60. We also analyzed the DA content and its metabolites, dopac (DOPAC) and homovanillic acid (HVA) by HPLC using reverse phase chromatography coupled with electrochemical detection in NAc, striatum(STR) and PFc at PND28 and 60.We only found a significant decreased in DA and HVA content in striatum at PND60 but no changes were observed in NAc at both ages. The increase of the specific dopaminergic TFs 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. Using techniques such as uptake assays, we evaluate DAT functionality at PND28 and 60.  We found and increased in NAc at PND28 and 60. The area selectivity of the increase of the TFs and DA uptake towards VTA and the mesolimbic pathway indicating that an insult received during the prenatal period will exert mainly motivational, emotional and reward behaviour impairments in the adult life.