Environmental enrichment reverted the upregulation of PDYN expression induced by prenatal ethanol exposure.

MIRANDA-MORALES, ROBERTO SEBASTIÁN; JIMENEZ-GARCIA, ANA MARIA; PAUTASSI, RICARDO MARCOS; WILLE-BILLE, ARANZA; D'ADDARIO, CLAUDIO

Córdoba

Conferencia; IX INTERNATIONAL MEETING of the Latin American Society for Biomedical Research on Alcoholism (LASBRA); 2019

LASBRA

Previous experiments showed that moderate prenatal exposure to ethanol (PEE) induces, in rats, alterations in anxiety response and adolescent voluntary ethanol consumption. Moreover, we identified an upregulation of kappa opioid system, that was accompanied with lower DNA methylation of these genes. This study assessed if rearing the litters (both dam and offspring) under environmental enrichment may inhibit the effects of PE.Pregnant Wistar rats received daily intragastric administration of ethanol 2.0 g/kg (PE group) or vehicle (PV group) in gestational days 17 to 20. From birth and until adolescence, the litters were housed in cages bigger than the standard, equipped with several objects that were rotated to keep them novel (environmental enrichment, EE), or in standard cages (non-enriched, NE). Gene expression of kappa opioid receptor (KOR) and the precursor of its ligand, prodynorphin (PDYN) was analyzed in several areas of mesocorticolimbic circuit of infant and adolescent offspring, as well as the DNA methylation of the promotor region of these genes. Moreover, we evaluated gene expression of BDNF in the same areas.PEE enhanced, in adolescents, the mRNA levels of PDYN at Ventral Tegmental Area (VTA), an effect that was inhibited by EE. This effect was associated with a lower DNA methylation in the PE-NE group. KOR gene expression at the Nucleus Accumbens (AcbN) was lower in PE vs PV subject. In Amygdala (AMY), PE-NE infants expressed higher levels of KOR, but this effect was not related to DNA methylation changes.We observed a PEE-induced downregulation of BDNF gene expression in VTA and Prefrontal Cortex (PFC).These results are suggestive of a PEE-induced upregulation of the KOR transmitter system that, at least in certain sites, seem to be regulated by alterations in epigenetic molecular mechanisms. Environmental enrichment could be a promising therapeutic to inhibit these detrimental effects of PEE.