Direct analyses of changes in the activity or levels of various proteins in the brains of alcoholics and other drug addicts also can provide insight into the neurobiology of addiction. Such studies found the following: Postmortem studies of the brains of human alcoholics indicate that the innate immune chemokine MCP-1 is increased severalfold in multiple brain regions (Breese et al. 2008). Consistent with this, chronic alcohol treatment of mice (Qin et al. 2008) or of cultured brain slices from the rat hippocampus (Zou and Crews 2010) also increases expression of MCP-1 and other innate immune genes.Proteins that serve as markers of microglial activation are increased across the alcoholic brain (He and Crews 2008).Consistent with alcoholism being related to neuroimmune signaling, postmortem studies of gene expression in the brains of human alcoholics found increased levels of a subunit of NF-κB; moreover, 479 genes targeted by NF-κB showed increased expression in the frontal cortex of alcoholics (Okvist et al. 2007).Postmortem analyses of alcoholic human brain gene expression found innate immune activation of cell adhesion and extracellular membrane components of innate immune gene signaling (Liu et al. 2006).
