Developmental alcohol exposure models consistently report widespread cell death in the brain following even a single administration of alcohol, with third trimester-equivalent models demonstrating the most vulnerability. While apoptosis is a naturally-occurring phenomenon in the developing brain (Johnston, 2009; Rakic and Zecevic, 2000), alcohol induces massive waves of apoptosis, particularly in brain regions undergoing significant growth when alcohol is administered (Farber et al., 2010; Ikonomidou et al., 2000; Olney et al., 2002). Recent work substantiates that epigenetics play a role in controlling alcohol-induced cell death. Third trimester-equivalent (PD7) alcohol alters levels of DNMTs (Nagre et al., 2015) in a caspase-3-dependent manner, linking methyltransferase activity with apoptotic processes that could result in long-term regional volumetric or functional deficits in the alcohol-exposed brain. One proposed pathway through which alcohol stimulates apoptosis is induction of oxidative stress pathways. Oxidative stress damages cells and 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
