Postnatal toxicant exposure in 3xTgAD mice promotes gene x environment-related early alterations to neuroimmune epigenetic profiles

Abstract

Aim: The purpose of this study was to evaluate sex-biased, maladaptive changes to epigenetic regulation critical for development of neuroimmune crosstalk resulting from an early-life toxicant exposure previously associated with increased susceptibility to later-life neurodegeneration. Methods: An evaluation of early-life gene x environment (GxE) interactions was performed in a mouse model of Alzheimer’s disease (Tg) orally exposed to lead acetate (Pb) from postnatal day (PND) 5-9. Following exposure, immunohistochemical analysis was used to evaluate hippocampal expression of DAP12, a marker for perinatal microglia related to microglial-mediated postnatal synaptic pruning of neurons. Altered profiles of three microRNAs critical to homeostatic microglia: neuron signaling (miR-34a, miR-124, miR-132) were measured by