Cited by 183Neuroinflammation and Neurodegeneration MechanismsSubstance Abuse Treatment and OutcomesAlcohol Consumption and Health Effects

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Adolescent binge drinking increases expression of the danger signal receptor agonist HMGB1 and toll-like receptors in the adult prefrontal cortex

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Vetreno, R.P., Crews, F.T.·2012·Neuroscience

DOI 10.1016/j.neuroscience.2012.08.046PMC PMC3740555

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Abstract

Adolescence is a critical developmental stage of life during which the prefrontal cortex (PFC) matures, and binge drinking and alcohol abuse are common. Recent studies have found that ethanol increases neuroinflammation via upregulated high-mobility group box 1 (HMGB1) signaling through Toll-like receptors (TLRs). HMGB1/TLR 'danger signaling' induces multiple brain innate immune genes that could alter brain function. To determine whether adolescent binge drinking persistently increases innate immune gene expression in the PFC, rats (P25-P55) were exposed to adolescent intermittent ethanol (AIE [5.0 g/kg, 2-day on/2-day off schedule]). On P56, HMGB1/TLR danger signaling was assessed using immunohistochemistry (i.e., +immunoreactivity [+IR]). In a separate group of subjects, spatial and reversal learning on the Barnes maze was assessed in early adulthood (P64-P75), and HMGB1/TLR danger signaling was measured using immunohistochemistry for +IR and RT-PCR for mRNA in adulthood (P80). Immunohistochemical assessment at P56 and 24 days later at P80 revealed increased frontal cortical HMGB1, TLR4, and TLR3 in the AIE-treated rats. Adolescent intermittent ethanol treatment did not alter adult spatial learning on the Barnes maze, but did cause reversal learning deficits and increased perseverative behavior. Barnes maze deficits correlated with the expression of danger signal receptors in the PFC. Taken together, these findings provide evidence that adolescent binge drinking leads to persistent upregulation of innate immune danger signaling in the adult PFC that correlates with adult neurocognitive dysfunction.

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Crews FT, Qin L, Sheedy D, Vetreno RP, Zou J (in press) HMGB1/TLR receptor danger signaling increases brain neuroimmune activation in alcohol dependence. Biol Psychiatry.
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Authors: Vetreno, R. P., & Crews, F. T.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Vetreno, R.P.
ORCID: Vetreno, R.P.
Crews, F.T.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2012-12
Volume: 226
Pages: 475-488
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2012.08.046
PMC: PMC3740555
OpenAlex: W2089714619
Cited by: 183
References: 66
Citations by year: 2026: 8 · 2025: 9 · 2024: 13 · 2023: 8 · 2022: 16 · 2021: 23 · 2020: 14 · 2019: 14 · 2018: 9 · 2017: 20 · 2016: 15 · 2015: 15 · 2014: 11 · 2013: 8
FWCI: 5.18
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: Center for Alcohol Studies
National Institutes of Health (AA-11605, AA007573, AA019767)
National Institute on Alcohol Abuse and Alcoholism (P50AA011605, AA 11605, U24AA020022, U01AA020023, AA020023, L40 AA021590, AA021040, AA 007573, F32AA021040, AA020022, AA020024, U24AA020024, U54AA019767, AA019767, P60AA011605, T32AA007573)
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords: adolescent binge drinking, prefrontal cortex, HMGB1, danger signaling, TLR4, TLR3, neuroinflammation, innate immunity, spatial learning, perseveration, neurocognitive impairment, alcohol abuse
MeSH terms: Adolescent, Animals, Cognition Disorders, Female, Fluorescent Antibody Technique, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Reversal Learning, Rats, Wistar, Prefrontal Cortex, Microscopy, Confocal, Maze Learning, HMGB1 Protein, Toll-Like Receptors, Toll-Like Receptor 3, Toll-Like Receptor 4, Rats, Real-Time Polymerase Chain Reaction, Binge Drinking

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Adolescent binge drinking increases expression of the danger signal receptor agonist HMGB1 and toll-like receptors in the adult prefrontal cortex

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