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Alcohol, HMGB1, and Innate Immune Signaling in the Brain
Fulton T Crews1,2,3, Leon G Coleman1,2, Victoria A Macht1
1Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Alcohol Research : Current Reviews
|August 13, 2024
Summary
High mobility group box protein 1 (HMGB1) and Toll-like receptor (TLR) signaling are key in alcohol use disorder (AUD) development. Targeting these neuroimmune pathways may offer new treatments for alcohol misuse.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Binge drinking in adolescence can lead to compulsive alcohol use and alcohol use disorder (AUD).
- Neuroimmune signaling plays a critical role in alcohol-induced changes in brain function, mood, and neurodegeneration.
- High mobility group box protein 1 (HMGB1) and Toll-like receptor (TLR) signaling are implicated in alcohol's effects on the brain.
Purpose of the Study:
- To present a mechanistic hypothesis on the role of HMGB1 and TLR signaling in alcohol-induced neuroimmune responses.
- To explore how these pathways contribute to the development of alcohol use disorder (AUD).
- To guide future research for prevention and treatment strategies for AUD.
Main Methods:
- A literature review was conducted using PubMed, Scopus, and Embase databases.
- Search terms included "HMGB1 protein," "alcohol," and "brain."
- Articles published between 1991 and 2023 were included, with approximately 100 articles analyzed.
Main Results:
- HMGB1 activates pro-inflammatory signals via TLRs, contributing to brain adaptations in response to binge and chronic heavy drinking.
- Ethanol exposure increases HMGB1 levels in both blood and brain.
- Adolescent intermittent ethanol (AIE) binge drinking in rats persistently elevates brain HMGB1, alters microglia and neuronal networks, and exacerbates alcohol intake and anxiety.
Conclusions:
- Elevated HMGB1 and TLRs are found in postmortem AUD brains, suggesting a role in human alcohol-related pathology.
- Microglia activation by binge drinking influences synaptic regulation and contributes to AUD risk.
- Interventions targeting HMGB1 and inflammation, such as anti-inflammatory drugs and HMGB1 antagonists, show potential for treating alcohol misuse and AUD.
