This study presents a global picture of differences between alcoholics and controls in gene expression in the post mortem hippocampus. A major theme that emerges from the data is that the hippocampus in alcoholics shows dramatic signs of stress. Genes and pathways (Table 2) involved in stress responses are mostly increased in alcoholics. Metallothioneins, a large number of which are increased in the hippocampus (Table 1E), are increased in many stress conditions (Aschner & West, 2005). EIF2 signaling, which is increased, functions to resolve endoplasmic reticulum (ER) stress; if ER stress cannot be resolved, apoptosis can result (Lerner et al., 2012). TXNIP (1.7-fold higher in alcoholics) can be transcriptionally induced by TGFβ1 and glucocorticoids (Chen et al., 2010; Han et al., 2003), and can link oxidative stress to inflammation via the NLRP3 inflammasome (NLR family, pyrin domain containing 3) (Zhou et al., 2010), an upstream activator of NF-κB signaling that plays a role in the regulation of inflammation, the immune response, and apoptosis.
