ArticleNature metabolism2021
Brain ethanol metabolism by astrocytic ALDH2 drives the behavioural effects of ethanol intoxication.
Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 109 citations in OpenAlex.
- Spinal neuronal TLR4-induced enhancement of nociceptive signals contributes to myocardial ischemia/reperfusion injury.Basic research in cardiology · 2026Article
- Glial-neuronal crosstalk via GABA signaling: mechanistic insights into neuropsychiatric and neurological pathophysiology.Molecular psychiatry · 2026Review
- Pharmacological Inhibition of HDAC6 Transiently Reduces Voluntary Ethanol Consumption in Male Mice.Alcohol, clinical & experimental research · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- Astrocytic NLRP6 inflammasome: From protective sentinels to drivers of alcohol-induced neuroinflammation.Neural regeneration research · 2026Article
- Protocol for metabolite extraction and sample preparation from primary astrocytes for mass spectrometry-based metabolomic analysis.STAR protocols · 2026Article
- Age and Sex Differences in Alcohol Withdrawal Syndrome.Mayo Clinic proceedings. Innovations, quality & outcomes · 2026Article
- From target specificity to metabolic efficiency: Design and optimization of etomidate analogues for potential improvement in postoperative outcomes.Acta pharmaceutica Sinica. B · 2026Article
- ALDH2-mediated GABA biosynthesis regulates hippocampal LTP and learning adaptability.Nature chemical biology · 2026Article
- Adolescent Binge Ethanol Exposure Confers Lasting Adult Alcohol Tolerance due to Neuroimmune Activation: Reversal by Inhibition of HMGB1.Addiction biology · 2026Article
- Astrocytic connexins in alcohol use disorder: mechanisms of neuroinflammation and therapeutic potential.Frontiers in psychiatry · 2026Review
- Spinal glycine receptor alpha 1 coordinates startle behavior through a cell-type specific mechanism.International journal of biological sciences · 2026Article
- Astrocytes and Alcohol Throughout the Lifespan.Biological psychiatry · 2026Review
- Hepatic Aquaporin 8 Promotes Alcohol Consumption and Ameliorates Alcohol-Induced Liver Injury by Facilitating Acetaldehyde Excretion.International journal of biological sciences · 2026Article
- Adolescent intermittent ethanol exposure produces sex-specific development of functional tolerance to ethanol-induced motor impairment and hypothermia.Neuropharmacology · 2025Article
- Transcriptome of monocytes from liver, brain and bone marrow reveals organ-specific features in aging and alcohol misuse.JHEP reports : innovation in hepatology · 2025Article
- Selectively counteracting cerebellar adaptations to chronic alcohol exposure reduces acute alcohol withdrawal severity in C57BL6/N mice.Neuropharmacology · 2025Article
- Alcohol, aging, and the gut microbiome: Intersections of immunity, barrier dysfunction, and disease.Alcohol (Fayetteville, N.Y.) · 2025Review
- Alcohol addiction and Alzheimer's disease: a molecular collision course.Translational psychiatry · 2025Review
- Recent advances in alcohol metabolism: from the gut to the brain.Physiological reviews · 2025Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Alcohol is among the most widely used psychoactive substances worldwide. Ethanol metabolites such as acetate, thought to be primarily the result of ethanol breakdown by hepatic aldehyde dehydrogenase 2 (ALDH2), contribute to alcohol's behavioural effects and alcoholism. Here, we show that ALDH2 is expressed in astrocytes in the mouse cerebellum and that ethanol metabolism by astrocytic ALDH2 mediates behavioural effects associated with ethanol intoxication. We show that ALDH2 is expressed in astrocytes in specific brain regions and that astrocytic, but not hepatocytic, ALDH2 is required to produce ethanol-derived acetate in the mouse cerebellum. Cerebellar astrocytic ALDH2 mediates low-dose ethanol-induced elevation of GABA levels, enhancement of tonic inhibition and impairment of balance and coordination skills. Thus, astrocytic ALDH2 controls the production, cellular and behavioural effects of alcohol metabolites in a brain-region-specific manner. Our data indicate that astrocytic ALDH2 is an important, but previously under-recognized, target in the brain to alter alcohol pharmacokinetics and potentially treat alcohol use disorder.
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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.