Gestational stress consequences on prepubertal male offspring behavior are possibly mediated by epigenetic changes in the hippocampus

PASTOR, VERÓNICA; BROCCO, MARCELA; PALLARÉS, MARÍA EUGENIA; ALZAMENDI A; ANTONELLI, MARTA CRISTINA; MONTELEONE, MELISA; OLSZEVICKI, SANTIAGO

San Diego

Congreso; 46 th Annual Meeting of the Society for Neuroscience; 2016

Society for Neuroscience

Chronic stress increases the risk of developing depression and anxiety disorders. However, while some individuals develop such diseases, others can cope with traumatic stressors remaining unaffected. Variability in the stress response depends on the individual genetic and epigenetic background, and on the neonatal programming of the stress response system during early development. Maternal stress increases glucocorticoid levels which change gene and protein expression, affect fetus developing brain morphology and adult offspring behavior. We have previously demonstrated that prenatal stress (PS) induces persistent changes in the expression of plasticity-related genes such as gpm6a and bdnf in the offspring hippocampus. Here we evaluated gestational stress consequences on dams and on prepubertal male offspring behavior and stress response. Stressed dams showed lower body weight gain in comparison with unstressed control (C) rats, despite finding similar food and water intake between both experimental groups. At post-weaning stages stressed dams spent more time immobile in the open field and in the Porsolt test, pointing out that chronic stress during pregnancy increased depression-like behavior in the rat. Conversely, PS male offspring displayed a higher ratio in the open arms entries in an elevated plus maze, indicating a reduced anxiety-like behavior than C counterparts, and they also showed a reduced depression-like behavior (Porsolt test). Corticosterone levels did not differ between groups after an acute stress or 2h later. Overall, our findings indicate that although stress during pregnancy negatively affected the mother behavior, offspring did not show such effects. PS offspring seemed to perform better in the behavioral tests than C rats. Thus, we propose that exposure to an adverse intrauterine environment may provide individuals useful information to deal afterwards with harsh external conditions. This ?adaptive developmental plasticity? requires of persistent changes in gene expression. Since PS modulates the expression of the plasticity-related genes gpm6a and bdnf by changes in their methylation pattern, we propose that the methylation machinery (dnmts, methyl binding proteins, tets enzymes) could regulate the gene expression underlying the offspring behavior.