Epigenetic signature of prenatal stress on adult offspring

BILLI, S; MONTELEONE, MC; ANTONELLI, MC; BROCCO, MA; PALLARES, ME

Mar del Plata

Congreso; XXXII Congreso Annual SAN 2017; 2017

Prenatal stress (PS) strongly impacts on offspring, affecting gene expression and adult behavior. We studied the epigenetic signature (gene expression, microRNA levels, methylation status) in the hippocampus of adult offspring of pregnant rats subjected to PS. Our previous work showed that chronic stress alters the mRNA levels of GPM6A, a neuronal glycoprotein involved in filopodium extension. Now, we observed that PS also affects gpm6a expression. PS significantly modified the microRNA-133b levels, as well. Moreover, microRNA-133b was validated as a gpm6a regulator. In addition, PS significantly altered the bdnf, mef2a, suv39h1 and tet1 mRNA levels. Together with a reduced total 5-hydroxymetylcytosine content, our findings suggest that part of the long-lasting PS effects are linked to changes in plasticity genes and in the chromatin methylation pathway. Notably, PS altered the methylation pattern within two CpG islands in the gpm6a gene. PS-induced molecular changes alter neural connectivity, increasing the risk for neuropsychiatric disorders.Because of their antidepressant-like effects, histone deacetylase inhibitors (HDACi) are being broadly studied. We treated primary neuron cultures with the HDACi apicidin. It increased GPM6A expression and induced filopodium extension.In summary, PS affected the epigenetic machinery resulting in long-term effects. We propose gpm6a as a novel target for epigenetic regulation and for pharmacological manipulation to revert PS effects.