ArticleAlcoholism, clinical and experimental research2021
Increased Toll-like Receptor-MyD88-NFκB-Proinflammatory neuroimmune signaling in the orbitofrontal cortex of humans with alcohol use disorder.
Article in Alcoholism, clinical and experimental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- Alcohol drinking sex-dependently regulates interleukin-1 pro-inflammatory signaling in the prefrontal cortex of mice and rhesus macaques.Brain, behavior, and immunity · 2026Article
- Substance abuse and inflammation: consequences beyond the brain.Trends in immunology · 2026Review
- Epigenetic Repression of the Serotonergic Neuron Phenotype Following Adolescent Binge Drinking Is Restored through Inhibition of Proinflammatory Signaling by Exercise and Glycyrrhizic Acid.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- INTERFERON-REGULATORY FACTOR 7: A NEUROIMMUNE ROLE FOR VAPOR-INDUCED ESCALATIONS IN ETHANOL SELF-ADMINISTRATION.bioRxiv : the preprint server for biology · 2026Article
- Adolescent Binge Ethanol Exposure Confers Lasting Adult Alcohol Tolerance due to Neuroimmune Activation: Reversal by Inhibition of HMGB1.Addiction biology · 2026Article
- Early abstinence in severe alcohol use disorder: MCP-1 decline, choroid plexus shrinkage, and region-specific grey-matter volume changes.Translational psychiatry · 2026Article
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Alcohol, aging, and the gut microbiome: Intersections of immunity, barrier dysfunction, and disease.Alcohol (Fayetteville, N.Y.) · 2025Review
- Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.bioRxiv : the preprint server for biology · 2025Article
- Identification of Interleukin-1β in Whole Blood as a Candidate Biomarker for Alcohol Use Disorder Risk Based on AUDIT Scores.Addiction biology · 2025Article
- Loss of lysosomal acid lipase contributes to Alzheimer's disease pathology and cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Operant effort-based decision-making task reveals sex differences in motivational behavior but no long-term effects of adolescent intermittent ethanol in Sprague Dawley rats.Pharmacology, biochemistry, and behavior · 2025Article
- CAMK2D and Complement Factor I-Involved Calcium/Calmodulin Signaling Modulates Sodium Iodate-Induced Mouse Retinal Degeneration.Investigative ophthalmology & visual science · 2025Article
- Adolescent binge alcohol exposure accelerates Alzheimer's disease-associated basal forebrain neuropathology through proinflammatory HMGB1 signaling.Frontiers in aging neuroscience · 2025Article
- Impact of Neuroimmune System Activation by Adolescent Binge Alcohol Exposure on Adult Neurobiology.Advances in experimental medicine and biology · 2025Review
- Pharmacological characterization and preclinical evaluation of 11h: a novel, brain-penetrant PDE4 inhibitor for neurological disorders.Frontiers in pharmacology · 2025Article
- Toll-like receptor 7: A novel neuroimmune target to reduce excessive alcohol consumption.Neurobiology of stress · 2024Article
- Imaging neuroinflammation in individuals with substance use disorders.The Journal of clinical investigation · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMany brain disorders, including alcohol use disorder (AUD), are associated with induction of multiple proinflammatory genes. One aspect of proinflammatory signaling is progressive increases in expression across cells and induction of other innate immune genes. High-mobility group box 1 (HMGB1) heteromers contribute to amplification by potentiating multiple proinflammatory responses, including Toll-like receptors (TLRs). TLR signaling recruits coupling proteins linked to nuclear transcription factors that induce proinflammatory cytokines and chemokines and their respective receptors. We tested the hypothesis that AUD induction of TLR expression increases levels of proinflammatory genes and cellular signaling cascades in association with neurodegeneration in the orbitofrontal cortex (OFC).
methodsPostmortem human OFC tissue samples (n = 10) from males diagnosed with AUD were compared to age-matched moderate drinking controls (CON). Neuroimmune signaling molecules were assessed using immunohistochemistry for protein and reverse transcription polymerase chain reaction for messenger RNA (mRNA).
resultsIn the AUD OFC, we report induction of the endogenous TLR agonist HMGB1 as well as all TLRs assessed (i.e., TLR2-TLR9) except TLR1. This was accompanied by increased expression of the TLR adaptor protein myeloid differentiation primary response 88 (MyD88), activation of the proinflammatory nuclear transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and downstream induction of proinflammatory cytokines, chemokines, and their corresponding receptors. Several of these proinflammatory signaling markers are expressed in glia and neurons. The induction of HMGB1-TLR-MyD88-NFκB proinflammatory signaling pathways correlates with neurodegeneration (i.e., Fluoro-Jade B), lifetime alcohol consumption, and age of drinking onset.
conclusionThese data implicate the induction of HMGB1-TLR-MyD88-NFκB cascades through coordinated glial and neuronal signaling as contributors to the neurodegeneration seen in the postmortem human OFC of individuals with AUD.
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