ArticleJournal of neuroinflammation2017
Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
154 citing papers in PubMed, 2 syntheses or guidelines pooled it, 233 citations in OpenAlex.
- miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- The Role of High Mobility Group Box 1 (HMGB1) in Neurodegeneration: A Systematic Review.Current neuropharmacology · 2022Pooled it
- Targeting neuroinflammation with minocycline in heavy drinkers.Psychopharmacology · 2019Trial
- Pro-inflammatory microglia drive escalated alcohol consumption during early abstinence.bioRxiv : the preprint server for biology · 2026Article
- Ethanol exacerbates post-burn neuroinflammation and gut-brain barrier dysfunction which are associated with microbiome changes.Alcohol (Fayetteville, N.Y.) · 2026Review
- Intestinal and Blood-Brain Barrier Dysfunction in Lupus: Emerging Mechanisms and Modulation by Cinnamon.Molecules (Basel, Switzerland) · 2026Review
- Evolution of neutrophil extracellular traps in the pathology of stroke.Neural regeneration research · 2026Article
- Global deletion ofbioRxiv : the preprint server for biology · 2026Article
- Repeated TLR7 activation induces cell type- and brain region-specific transcriptome changes in male mice.Scientific reports · 2026Article
- Ethanol Alters the Neurexin Landscape in Human Neuroblastoma Cells.Alcohol, clinical & experimental research · 2026Article
- Psoriatic microRNAs induce NK cell activation via an innate immune crosstalk abrogated by the Toll-like receptor 7/8 antagonist Enpatoran.Journal of translational medicine · 2026Article
- Ethanol induces neuroimmune dysregulation and soluble TREM2 generation in a human iPSC neuron, astrocyte, microglia triculture model.Alcohol (Fayetteville, N.Y.) · 2026Article
- The Role of Neuro-Immune Regulation in the Pathogenesis of Psoriasis.Journal of immunology research · 2026Review
- Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol.The American journal of pathology · 2026Article
- Sex differences in the neuroimmune response following heavy, binge-like alcohol exposure in adolescent rats.Journal of neuroimmunology · 2025Article
- Purinergic and extracellular vesicle signaling in alcohol-induced blood-brain barrier breakdown and neuroimmune activation.Brain, behavior, and immunity · 2025Review
- Physiological Mechanisms Vulnerable to Alcohol-Induced Alterations: Role in Chronic Comorbidities.Comprehensive Physiology · 2025Review
- Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.bioRxiv : the preprint server for biology · 2025Article
- Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025Review
- Role of extracellular vesicle-carried ncRNAs in the interactive 'dialogue' within the brain and beyond: emerging theranostic epigenetic modifiers in brain-derived nanoplatforms.Translational neurodegeneration · 2025Review
94 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundToll-like receptor (TLR) signaling is emerging as an important component of neurodegeneration. TLR7 senses viral RNA and certain endogenous miRNAs to initiate innate immune responses leading to neurodegeneration. Alcoholism is associated with hippocampal degeneration, with preclinical studies linking ethanol-induced neurodegeneration with central innate immune induction and TLR activation. The endogenous miRNA let-7b binds TLR7 to cause neurodegeneration.
methodsTLR7 and other immune markers were assessed in postmortem human hippocampal tissue that was obtained from the New South Wales Tissue Bank. Rat hippocampal-entorhinal cortex (HEC) slice culture was used to assess specific effects of ethanol on TLR7, let-7b, and microvesicles.
resultsWe report here that hippocampal tissue from postmortem human alcoholic brains shows increased expression of TLR7 and increased microglial activation. Using HEC slice culture, we found that ethanol induces TLR7 and let-7b expression. Ethanol caused TLR7-associated neuroimmune gene induction and initiated the release let-7b in microvesicles (MVs), enhancing TLR7-mediated neurotoxicity. Further, ethanol increased let-7b binding to the danger signaling molecule high mobility group box-1 (HMGB1) in MVs, while reducing let-7 binding to classical chaperone protein argonaute (Ago2). Flow cytometric analysis of MVs from HEC media and analysis of MVs from brain cell culture lines found that microglia were the primary source of let-7b and HMGB1-containing MVs.
conclusionsOur results identify that ethanol induces neuroimmune pathology involving the release of let-7b/HMGB1 complexes in microglia-derived microvesicles. This contributes to hippocampal neurodegeneration and may play a role in the pathology of alcoholism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.