In Vivo and In Vitro Neuronal Plasticity Modulation by Epigenetic Regulators

Abstract

Prenatal stress (PS) induces molecular changes that alter neural connectivity, increasing the risk for neuropsychiatric disorders. Here we analyzed -in the hippocampus of adult rats exposed to PS- the epigenetic signature mediating the PS-induced neuroplasticity changes. Furthermore, using cultured hippocampal neurons, we investigated the effects on neuroplasticity of an epigenetic modulator. PS induced significant modifications in the mRNA levels of stress-related transcription factor MEF2A, SUV39H1 histone methyltransferase, and TET1 hydroxylase, indicating that PS modifies gene expression through chromatin remodeling. In in vitro analysis, histone acetylation inhibition with apicidin increased filopodium density, suggesting that the external regulation of acetylation levels might modulate neuronal morphology. These results offer a way to enhance neural connectivity that could be considered to revert PS effects.

Keywords: GPM6A; Histone deacetylase inhibitors; Hydroxymethylation; MEF2A; Primary hippocampal neurons; Rat.