This study demonstrates many differences in gene expression between the hippocampi of alcoholics and controls, and highlights interrelated insults to the hippocampus: stress, hypoxia, inflammation, and excess cortisol (Figures 2, 3). These may play roles in the demyelination, loss of glial cells, and decreased neurogenesis seen with chronic alcohol abuse. NF-κB appears to be a key player in these processes (Figure 3). Some of these differences in gene expression may be due to genetic variations that precede the addiction process and may play an active role in the addiction process. Others may be the result of years of excessive alcohol consumption, and still others may be altered due to the interaction of genetic variation with excessive alcohol consumption. A post mortem study such as this cannot distinguish among these possibilities. The modifications seen here in gene expression in these pathways could be part of the allostatic change suggested by Koob & Kreek (2007). In the hippocampus, resetting the cortisol pathway may be one way to break this chain of events. Decreased neurogenesis and increased inflammation are also seen in major
