genes within this pathway had reduced expression in the binge-drinking rats, including disheveled (Dvl2), Lrp1 (lipoprotein receptor 1), GSK3β and Tcf4 (Tables 2, 3). Tcf7l2, a member of the T-cell factor/lymphoid enhancer-binding factor family of high mobility group (HMG) box transcriptional activators, is decreased in expression in the vHip of the alcohol exposed animals; it is also the most inhibited gene in the upstream regulator analysis (Supplemental Table 2). Downstream targets of Tcf7l2 include genes involved in myelin production (e.g. Plp1, Mbp, Mag) (Lees & Brostoff, 1984; Norton & Cammer, 1984) and in synthesis of cholesterol (e.g. Hmgcs1, and indirectly, Hmgcr via its effect on the expression of Srepbf2). Hmgcr has decreased expression in the vHip (Table 2), which is necessary for myelination (Zhao et al., 2016). When β catenin combines with Tcf7l2, it controls the development and maturation of oligodendrocytes, and their production of myelin (Zhao et al. 2016). The somewhat larger fraction of differentially expressed genes characteristically enriched in oligodendrocytes that were decreased in the vHip (86%) compared to 79% overall, although only suggestive (p=0.09), may hint at a relative decrease in the number or activity of these critical cells. Previous work showed that expression of genes responsible
