ArticlePsychopharmacology2019
Ethanol induces interferon expression in neurons via TRAIL: role of astrocyte-to-neuron signaling.
Article in Psychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- EFFECTS OF TOLL-LIKE RECEPTOR 3 - DEPENDENT IMMUNE ACTIVATION IN MICE ARE SEX- AND TISSUE- SPECIFIC: IMPLICATIONS FOR ALCOHOL USE DISORDER.bioRxiv : the preprint server for biology · 2026Article
- A Comprehensive Review of poly(I: C) as a Tool for Investigating Astrocytic TLR3 Signaling.Neurochemical research · 2025Review
- The kynurenine pathway as a potential link between ethanol-induced behavioral alterations and neuroinflammation.Frontiers in pharmacology · 2025Article
- Ethanol Exacerbates the Alzheimer's Disease Pathology in the 5xFAD Mouse Model.Neuroglia (Basel, Switzerland) · 2024Article
- Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by AβJournal of neuroinflammation · 2024Article
- DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.Cell systems · 2024Article
- Alcohol, HMGB1, and Innate Immune Signaling in the Brain.Alcohol research : current reviews · 2024Review
- Review
- Sex-dependent factors of alcohol and neuroimmune mechanisms.Neurobiology of stress · 2023Article
- Increased Toll-like Receptor-MyD88-NFκB-Proinflammatory neuroimmune signaling in the orbitofrontal cortex of humans with alcohol use disorder.Alcoholism, clinical and experimental research · 2021Article
- Exosomes in Epilepsy of Tuberous Sclerosis Complex: Carriers of Pro-Inflammatory MicroRNAs.Non-coding RNA · 2021Article
- Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release.Nature communications · 2020Article
- Prospective Study Examining the Effects of Extreme Drinking on Brain Structure in Emerging Adults.Alcoholism, clinical and experimental research · 2020Article
- Effect of Cladribine on Neuronal Apoptosis: New Insight of In Vitro Study in Multiple Sclerosis Therapy.Brain sciences · 2020Article
- Machine learning-driven blood biomarker profiling and EGCG intervention in fetal alcohol spectrum disorder.International journal of clinical and health psychology : IJCHPArticle
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
rationaleAlcohol use disorder (AUD) involves dysregulation of innate immune signaling in brain. Toll-like receptor 3 (TLR3), an innate immune receptor that is upregulated in post-mortem human alcoholics, leads to induction of interferon (IFN) signaling. IFNs have been linked to depressive-like symptoms and therefore may play a role in addiction pathology. Astrocyte-neuronal signaling may contribute to maladaptation of neuronal circuits.
objectivesIn this manuscript, we examine ethanol (EtOH) induction of IFN signaling in neuronal, astrocyte, and microglial cell lines and assess astrocyte-neuronal interactions.
methodsU373 astrocytes, SH-SY5Y neurons, and BV2 microglia were treated with EtOH and analyzed for autocrine/paracrine IFN signaling.
resultsEtOH induced TLR3, IFNβ, and IFNγ in SH-SY5Y neurons and U373 astrocytes, but not in BV2 microglia. The IFN response gene TRAIL was also strongly upregulated by TLR3 agonist Poly(I:C) and EtOH in U373 astrocytes. TRAIL blockage via neutralizing antibody prevented induction of IFNs in SH-SY5Y neurons but not in U373 astrocytes. Blocking TRAIL in conditioned media from EtOH-treated astrocytes prevented induction of IFNs in SH-SY5Y neurons. Finally, an in vivo model of chronic 10-day binge EtOH exposure in C57BL6/J mice, as well as single acute treatment with Poly(I:C), showed increased TRAIL +IR cells in both orbitofrontal and entorhinal cortex.
conclusionsThis study establishes a role of astrocyte to neuron TRAIL release in EtOH-induced IFN responses. This may contribute to alcohol associated negative affect and suggest potential therapeutic benefit of TRAIL inhibition in AUD.
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