Stress-related behavior and hippocampal gene expression changes in male rats exposed to prenatal stress

VERÓNICA PASTOR; MELISA CAROLINA MONTELEONE; MARTA C ANTONELLI; MARÍA EUGENIA PALLARÉS; MARCELA ADRIANA BROCCO

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Prenatal stress (PS) is associated with a dysregulation of the offspring Stress System response and higher rates of mood disorders.We have previously demonstrated that PS induces persistent changes in the expression of plasticity-related genes in the offspringhippocampus, which is a brain structure that has a major role in stress regulation. In this work, we tested how the alteration in thegene-environment dialog induced by PS could induce long lasting consequences on offspring Stress System by epigenetic changesin the hippocampus. Pregnant Wistar rats received restraint stress during the third week of gestation (PS group) or left undisturbed(control group, C). Elevated plus maze, forced swimming test and stress reactivity to an acute stress were used to evaluate stress-related behaviors on male offspring. The test batteries began on postnatal day 28. After last behavioral test, hippocampi were dissected to assess the expression of candidate genes related to Stress System regulation and to DNA methylation pathways. We found that PS rats had decreased anxiety- (P=0.002) and depression-like behaviors (P=0.016) in comparison with C group. Gene expression of corticosteroid receptors (nr3c1 and nr3c2) and of chaperones that modulate their activity (fkbp4, fkbp5, bag1 and ppid) did not vary significantly between experimental groups. However, PS increased mRNA levels of chromatin remodeler genes (P=0.036 for dnmt3a; P=0.005 for mecp2; P=0.025 for tet1). Our findings highlight that the DNA methylation patterns, established by early-life experiences, may induce behavioral phenotypes which then dictate an individual?s reaction to new stressors encountered later in life. Because we found no relationship between offspring behavior and the expression of stress-related genes in the hippocampus, on-going studies are being directed to extend the analysis of the expression of these genes in further brain structures related to stress response.