Neuroimmune function and the consequences of alcohol exposure

Fulton T. Crews, Dipak K. Sarkar, Liya Qin, Jian Zou, Nadka Boyadjieva, Ryan P. Vetreno

Research output: Contribution to journalReview articlepeer-review

98 Scopus citations


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 neuro- biology of alcohol use disorder.

Original languageAmerican English
JournalAlcohol Research: Current Reviews
Issue number2
StatePublished - Jun 27 2015

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Clinical Psychology
  • Psychiatry and Mental health


  • Abuse and dependence
  • Alcohol effects and consequences
  • Alcohol exposure
  • Alcohol use
  • Binge drinking
  • Brain
  • Cytokines
  • Glutamate receptors
  • High-mobility group box 1
  • Immunity
  • Microglia
  • Neurodegeneration
  • Neuroimmune genes
  • Neuroimmune responses
  • Nuclear factor-kappa B
  • Oxidative stress
  • Stress axis
  • Stress responses
  • Toll-like receptors

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