Genomic and proteomic studies in humans have demonstrated alterations in gene expression and protein levels in alcoholics as opposed to nonalcoholic controls. In one study, genes for mitochondrial proteins were downregulated in the PFC of alcoholics and this was paralleled by an increase in repair proteins that are activated due to oxidative damage, possibly in response to mitochondrial dysfunction (Flatscher-Bader et al., 2005). There were also region-specific alterations in transcription factors and genes that encode DNA-binding proteins, protein trafficking, and apoptotic factors. Reverse transcription polymerase chain reaction (RT-PCR) analysis has demonstrated a downregulation in PCP4/PEP19, a gene that encodes for a protein that may have anti-apoptotic properties (Iwamoto et al., 2004). This study also showed alterations in expression of NEFH, which encodes a neurofilament protein, suggesting that changes in the expression of this protein could lead to altered organization of 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
