the cytoskeleton. Similar to animal studies, PFC tissue collected from chronic alcoholics shows changes in the expression of a number of genes involved in myelination (Mayfield et al., 2002). Levels of key energy-regulating and metabolism proteins are also downregulated in PFC white matter of alcoholics as opposed to nonalcoholic controls (Alexander-Kaufman et al., 2006). Other proteins show enhanced expression, including midkine, a repair protein, and EAAT1, a glutamate transporter (Flatscher-Bader and Wilce, 2008). Changes in midkine may indicate a response to oxidative damage after chronic alcohol use, whereas the change in transporter levels may be a compensatory mechanism in response to elevated levels of extracellular glutamate during withdrawal. Proteins related to the thiamine pathway that are involved in carbohydrate metabolism were down-regulated in the PFC of non-Wernicke-Korsokoff alcoholics (Matsumoto, 2009). The transcription factor NF-kappaB and its p50 subunit, which inhibit gene transcription, were also downregulated in postmortem prefrontal tissue of alcoholics as compared to controls, suggesting increased expression of genes related to synaptic plasticity that may play a role in the development and maintenance of alcohol dependence (Okvist et al., 2007). Taken together, these postmortem studies indicate a number of differences in the PFC of alcoholics that could lead to
