title: Neuroimmune Function and the Consequences of Alcohol Exposure.
abstract: Induction of neuroimmune genes by binge drinking increases neuronal excitability and oxidative stress, contributing to the neurobiology of alcohol dependence and causing neurodegeneration. Ethanol exposure activates signaling pathways featuring high-mobility group box 1 and Toll-like receptor 4 (TLR4), resulting in induction of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells, which regulates expression of several cytokine genes involved in innate immunity, and its target genes. This leads to persistent neuroimmune responses to ethanol that stimulate TLRs and/or certain glutamate receptors (i.e., N-methyl-d-aspartate receptors). Alcohol also alters stress responses, causing elevation of peripheral cytokines, which further sensitize neuroimmune responses to ethanol. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of alcohol abuse have identified significant frontal cortical degeneration and loss of hippocampal neurogenesis, consistent with neuroimmune activation pathology contributing to these alcohol-induced, long-lasting changes in the brain. These alcohol-induced long-lasting increases in brain neuroimmune-gene expression also may contribute to the neurobiology of alcohol use disorder.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Fulton T
authors.initials: FT
authors.lastname: Crews
authors.affiliation: Rutgers University, New Brunswick, New Jersey.
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Sarkar
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Liya
authors.initials: L
authors.lastname: Qin
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey.
authors.forename: Nadka
authors.initials: N
authors.lastname: Boyadjieva
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Vetreno
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000437:Alcoholism / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D017628:Microglia / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000235:genetics / Q000276:immunology*; D018384:Oxidative Stress / Q000276:immunology*; D017470:Receptors, Glutamate / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; D016328:NF-kappa B; D017470:Receptors, Glutamate; D051193:Toll-Like Receptors