DNA through the production of peroxidases and other free radical molecules. PAE increased levels of reactive oxygen species (ROS) and apoptosis in fetal rat cortical neurons, while antioxidant pretreatment of the cells prevented the apoptosis, meaning ROS production directly contributed to increased alcohol-induced cell death (Ramachandran et al., 2003). Lipid peroxidase was also upregulated throughout the brain for up to 12 weeks following postnatal alcohol exposure (Petkov et al., 1992) and until at least postnatal day (PD) 60 following perinatal exposure (Brocardo et al., 2012). Perinatal alcohol also increased protein oxidation in the hippocampus and cerebellum and increased anxiety- and depressive-like behaviors in the mice. While oxidative stress itself is not an epigenetic modification, recent evidence suggests that postnatal alcohol exposure might regulate oxidative pathways through long-term methylation and gene expression changes in genes related to oxidative stress in the adult mouse hippocampus (Chater-Diehl et al., 2016). Epigenetic regulation of signaling pathways related to free radical scavenging and peroxisome function could be one avenue through which developmental alcohol exposure produces long-term impairments in cellular processes and behavioral output.
