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Neuroimmune Function and the Consequences of Alcohol Exposure

View Article: PubMed Central

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.

No MeSH data available.


Microglial activation, as indicated by expression of the microglial marker Iba-1, is increased in postmortem alcoholic brain. The photomicrographs depict microglia from postmortem brain samples of alcoholics and control subjects. The number of Iba-1–positive microglia (dark stains) is higher in the alcoholic than in the control samples. SOURCE: He and Crews 2008.
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f2-arcr-37-2-331: Microglial activation, as indicated by expression of the microglial marker Iba-1, is increased in postmortem alcoholic brain. The photomicrographs depict microglia from postmortem brain samples of alcoholics and control subjects. The number of Iba-1–positive microglia (dark stains) is higher in the alcoholic than in the control samples. SOURCE: He and Crews 2008.

Mentions: Some studies found an increase in the expression of the microglial marker Iba-1 in the brains of alcoholic individuals (see figure 2) (He and Crews 2008), suggesting that microglia contribute to the neurobiology of alcoholism. Microglia in postmortem human alcoholic brain and chronic alcohol-treated mouse and rat brain show increased MHC gene expression, but not the bushy or phagocytic activation profiles associated with marked brain damage. Chronic ethanol treatment also increases microglial TLR4 expression (Vetreno et al. 2013). Thus, microglia are the only immune cells in healthy brain and are integrated into the brain’s responses to both neurotransmitters and neuroimmune signals. They also seem to contribute to chronic alcohol-induced responses.


Neuroimmune Function and the Consequences of Alcohol Exposure
Microglial activation, as indicated by expression of the microglial marker Iba-1, is increased in postmortem alcoholic brain. The photomicrographs depict microglia from postmortem brain samples of alcoholics and control subjects. The number of Iba-1–positive microglia (dark stains) is higher in the alcoholic than in the control samples. SOURCE: He and Crews 2008.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590627&req=5

f2-arcr-37-2-331: Microglial activation, as indicated by expression of the microglial marker Iba-1, is increased in postmortem alcoholic brain. The photomicrographs depict microglia from postmortem brain samples of alcoholics and control subjects. The number of Iba-1–positive microglia (dark stains) is higher in the alcoholic than in the control samples. SOURCE: He and Crews 2008.
Mentions: Some studies found an increase in the expression of the microglial marker Iba-1 in the brains of alcoholic individuals (see figure 2) (He and Crews 2008), suggesting that microglia contribute to the neurobiology of alcoholism. Microglia in postmortem human alcoholic brain and chronic alcohol-treated mouse and rat brain show increased MHC gene expression, but not the bushy or phagocytic activation profiles associated with marked brain damage. Chronic ethanol treatment also increases microglial TLR4 expression (Vetreno et al. 2013). Thus, microglia are the only immune cells in healthy brain and are integrated into the brain’s responses to both neurotransmitters and neuroimmune signals. They also seem to contribute to chronic alcohol-induced responses.

View Article: PubMed Central

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.

No MeSH data available.