Subsequent studies focusing on the prefrontal cortex, specifically the orbital frontal cortex (OFC), found increased levels of HMGB1 as well as TLRs (specifically TLR2, TLR3, and TLR4) in postmortem alcoholic brain (Crews et al. 2013). Furthermore, NADPH oxidase was increased in alcoholic OFC, consistent with increased oxidative stress as found in mice. The HMGB1 receptor RAGE also was increased in postmortem human alcoholic brain (Vetreno et al. 2013). Finally, studies detected increased IL-1β inflammasome markers in the hippocampus of postmortem alcoholic brains that could contribute to loss of neurogenesis. These observations indicate that multiple neuro-immune genes are increased in alcoholic brain and likely contribute to neurodegeneration and the neurobiology of alcoholism in humans.
