ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2014
P2X4 receptor regulates alcohol-induced responses in microglia.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Ivermectin reduces withdrawal-induced alcohol intake in rats: Association with CeA GABAergic enhancement and P2rx4 genetic liability.Neuropharmacology · 2026Article
- Ivermectin Reduces Withdrawal-Induced Alcohol Intake via CeA GABAergic Enhancement.bioRxiv : the preprint server for biology · 2025Article
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- Review
- The neuroimmune system - Where aging and excess alcohol intersect.Alcohol (Fayetteville, N.Y.) · 2023Review
- Article
- The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target.International journal of molecular sciences · 2022Review
- Beyond Genes: Inclusion of Alternative Splicing and Alternative Polyadenylation to Assess the Genetic Architecture of Predisposition to Voluntary Alcohol Consumption in Brain of the HXB/BXH Recombinant Inbred Rat Panel.Frontiers in genetics · 2022Article
- Interactions of neuroimmune signaling and glutamate plasticity in addiction.Journal of neuroinflammation · 2021Review
- Structural and Functional Features of the P2X4 Receptor: An Immunological Perspective.Frontiers in immunology · 2021Review
- Microglia Phenotypes Following the Induction of Alcohol Dependence in Adolescent Rats.Alcoholism, clinical and experimental research · 2021Article
- Implication of Neuronal Versus Microglial P2X4 Receptors in Central Nervous System Disorders.Neuroscience bulletin · 2020Review
- Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations.Journal of neuroinflammation · 2020Article
- Nanoparticle-Mediated Therapeutic Application for Modulation of Lysosomal Ion Channels and Functions.Pharmaceutics · 2020Review
- Characterization of the SIM-A9 cell line as a model of activated microglia in the context of neuropathic pain.PloS one · 2020Article
- Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders.Psychopharmacology · 2018Review
- Transcriptome analysis of alcohol-treated microglia reveals downregulation of beta amyloid phagocytosis.Journal of neuroinflammation · 2018Article
- Reduced expression of purinergic P2X4 receptors increases voluntary ethanol intake in C57BL/6J mice.Alcohol (Fayetteville, N.Y.) · 2018Article
- Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells.Neuropharmacology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mounting evidence indicates that alcohol-induced neuropathology may result from multicellular responses in which microglia cells play a prominent role. Purinergic receptor signaling plays a key role in regulating microglial function and, more importantly, mediates alcohol-induced effects. Our findings demonstrate that alcohol increases expression of P2X4 receptor (P2X4R), which alters the function of microglia, including calcium mobilization, migration and phagocytosis. Our results show a significant up-regulation of P2X4 gene expression as analyzed by real-time qPCR (***p < 0.002) and protein expression as analyzed by flow cytometry (**p < 0.004) in embryonic stem cell-derived microglial cells (ESdM) after 48 hours of alcohol treatment, as compared to untreated controls. Calcium mobilization in ethanol treated ESdM cells was found to be P2X4R dependent using 5-BDBD, a P2X4R selective antagonist. Alcohol decreased migration of microglia towards fractalkine (CX3CL1) by 75 % following 48 h of treatment compared to control (***p < 0.001). CX3CL1-dependent migration was confirmed to be P2X4 receptor-dependent using the antagonist 5-BDBD, which reversed the effects as compared to alcohol alone (***p < 0.001). Similarly, 48 h of alcohol treatment significantly decreased phagocytosis of microglia by 15 % compared to control (*p < 0.05). 5-BDBD pre-treatment prior to alcohol treatment significantly increased microglial phagocytosis (***p < 0.001). Blocking P2X4R signaling with 5-BDBD decreased the level of calcium mobilization compared to ethanol treatment alone. These findings demonstrate that P2X4 receptor may play a role in modulating microglial function in the context of alcohol abuse.
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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.