The vHip, but not the mPFC, shares some pathways with the DRN and PAG (Supplemental Table 4), including cAMP-mediated signaling, protein kinase A signaling, CREB signaling in neurons, Gαq signaling, and calcium signaling. The decrease in expression of Hmgcr and Srepbf2 (genes important in cholesterol synthesis) in the vHip was paralleled by decreases in genes important in cholesterol synthesis and myelination in both the DRN and PAG of these animals (McClintick et al., 2015, 2016), and also in human post-mortem tissue (Liu et al., 2006; Mayfield et al., 2002; McClintick et al., 2013). Tcf7l2, which can control cholesterol production along with oligodendrocyte maturation, was decreased in vHip and PAG, and both of these regions have a disproportionate number of oligodendrocyte enriched genes with decreased expression. Genes necessary for cholesterol production were also decreased in expression. While myelin was not measured in these animals, these three lines of evidence suggest decreases in myelination in the binge-drinking animals. Alcohol consumption has resulted in decreased or poor myelination in other rat lines and in humans (Vargas et al., 2014, Jacobus & Tapert, 2013).
