Epigenetic siganture of prenatal stress in adult offspring

BROCCO MARCELA ADRIANA; MONTELEONE, MELISA C; PALLARÉS, MARÍA EUGENIA; ANTONELLI, MARTA C

Mar del Plata

Simposio; Sociedad Argentina de Neurociencias; 2017

Prenatalstress (PS) strongly impacts on offspring, affecting gene expression and adult behavior.We studied the epigenetic signature (gene expression, microRNA levels, methylation status) in the hippocampusof adult offspring of pregnant rats subjected to PS. Our previous work showedthat chronic stress alters the mRNA levels of GPM6A, a neuronal glycoproteininvolved in filopodium extension. Now, we observed that PS also affects gpm6aexpression. 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 total5-hydroxymetylcytosine content, our findings suggest thatpart of the long-lasting PS effects are linked to changes in plasticity genes andin the chromatin methylation pathway. Notably, PS altered the methylation pattern within twoCpG islands in the gpm6a gene. PS-inducedmolecular changes alter neuralconnectivity, increasing the risk for neuropsychiatric disorders. Becauseof their antidepressant-like effects, histone deacetylase inhibitors (HDACi) are being broadly studied. Wetreated primary neuron cultures with the HDACi apicidin. It increased GPM6Aexpression and induced filopodium extension. In summary, PSaffected the epigenetic machinery resultingin long-term effects. We propose gpm6a as a novel target forepigenetic regulation and for pharmacologicalmanipulation to revert PS effects.