The role of neuroimmune signaling in alcoholism.
Alcohol consumption and stress increase brain levels of known innate immune signaling molecules. Microglia, the innate immune cells of the brain, and neurons respond to alcohol, signaling through Toll-like receptors (TLRs), high-mobility group box 1 (HMGB1), miRNAs, pro-inflammatory cytokines and their associated receptors involved in signaling between microglia, other glia and neurons. Repeated cycles of alcohol and stress cause a progressive, persistent induction of HMGB1, miRNA and TLR receptors in brain that appear to underlie the progressive and persistent loss of behavioral control, increased impulsivity and anxiety, as well as craving, coupled with increasing ventral striatal responses that promote reward seeking behavior and increase risk of developing alcohol use disorders. Studies employing anti-oxidant, anti-inflammatory, anti-depressant, and innate immune antagonists further link innate immune gene expression to addiction-like behaviors. Innate immune molecules are novel targets for addiction and affective disorders therapies. This article is part of the Special Issue entitled "Alcoholism".
University of North Carolina, Chapel Hill School of Medicine, Bowles Center for Alcohol Studies, CB# 7178 UNC-CH, Chapel Hill, NC 27599, USA.
Fulton T
FT
Crews
University of North Carolina, Chapel Hill School of Medicine, Bowles Center for Alcohol Studies, CB# 7178 UNC-CH, Chapel Hill, NC 27599, USA.
Colleen J
CJ
Lawrimore
University of North Carolina, Chapel Hill School of Medicine, Bowles Center for Alcohol Studies, CB# 7178 UNC-CH, Chapel Hill, NC 27599, USA.
T Jordan
TJ
Walter
University of North Carolina, Chapel Hill School of Medicine, Bowles Center for Alcohol Studies, CB# 7178 UNC-CH, Chapel Hill, NC 27599, USA. Electronic address: leon_coleman@med.unc.edu.
Leon G
LG
Coleman
D000437:Alcoholism / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D016739:Behavior, Addictive / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000378:metabolism*; D004660:Encephalitis / Q000150:complications / Q000276:immunology / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D015213:Neuroimmunomodulation; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
D024243:HMGB1 Protein; D051193:Toll-Like Receptors
Addiction; Alcohol; Azithromycin (PubChem CID: 447043); Cytokines; Glycyrrhizin (PubChem CID: 14982); HMGB1; Ibudilast (PubChem CID: 3671); Indomethacin (PubChem CID: 3715); Minocycline (PubChem CID: 54675783); Naltrexone (PubChem CID: 5360515); Pioglitazone (PubChem CID: 4829); Rapamycin (PubChem CID: 5284616); Rifampin (PubChem CID: 5381226); Simvastatin (PubChem CID: 54454); TLR; miRNA-let-7