ArticleThe international journal of neuropsychopharmacology2021
Epigenetic Regulation of GABAergic Neurotransmission and Neurosteroid Biosynthesis in Alcohol Use Disorder.
Article in The international journal of neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Multi-omics and electrophysiological examination of GABAMolecular psychiatry · 2026Article
- Benefits and Limitations Associated with the Use of Alternative Biological Matrices in Forensic Toxicology, as Well as Genetic Markers of Poisoning and Psychoactive Substance Abuse.International journal of molecular sciences · 2026Review
- Crosstalk Between Gut Microbiota, Epigenome, and Neurotransmitters in Health and Disease.Cells · 2026Review
- Evaluating and Determining the Effects of Psychotropic Drugs on Motor Vehicle Driving Performance: Key Considerations of the Japanese Guideline and Criteria for Clinical Implementation of Evidence.Neuropsychopharmacology reports · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.Frontiers in neuroendocrinology · 2024Review
- Functional roles, regulatory mechanisms and theranostics applications of ncRNAs in alcohol use disorder.International journal of biological sciences · 2023Review
- Is DNA methylation in the brain a mechanism of alcohol use disorder?Frontiers in behavioral neuroscience · 2023Review
- Neurosteroids (allopregnanolone) and alcohol use disorder: From mechanisms to potential pharmacotherapy.Pharmacology & therapeutics · 2022Review
- Understanding Immune-Driven Brain Aging by Human Brain Organoid Microphysiological Analysis Platform.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Immune treatments for alcohol use disorder: A translational framework.Brain, behavior, and immunity · 2021Review
- PPAR-α Hypermethylation in the Hippocampus of Mice Exposed to Social Isolation Stress Is Associated with Enhanced Neuroinflammation and Aggressive Behavior.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAlcohol use disorder (AUD) is a chronic relapsing brain disorder. GABAA receptor (GABAAR) subunits are a target for the pharmacological effects of alcohol. Neurosteroids play an important role in the fine-tuning of GABAAR function in the brain. Recently, we have shown that AUD is associated with changes in DNA methylation mechanisms. However, the role of DNA methylation in the regulation of neurosteroid biosynthesis and GABAergic neurotransmission in AUD patients remains under-investigated.
methodsIn a cohort of postmortem brains from 20 male controls and AUD patients, we investigated the expression of GABAAR subunits and neurosteroid biosynthetic enzymes and their regulation by DNA methylation mechanisms. Neurosteroid levels were quantified by gas chromatography-mass spectrometry.
resultsThe α 2 subunit expression was reduced due to increased DNA methylation at the gene promoter region in the cerebellum of AUD patients, a brain area particularly sensitive to the effects of alcohol. Alcohol-induced alteration in GABAAR subunits was also observed in the prefrontal cortex. Neurosteroid biosynthesis was also affected with reduced cerebellar expression of the 18kDa translocator protein and 3α-hydroxysteroid dehydrogenase mRNAs. Notably, increased DNA methylation levels were observed at the promoter region of 3α-hydroxysteroid dehydrogenase. These changes were associated with markedly reduced levels of allopregnanolone and pregnanolone in the cerebellum.
conclusionGiven the key role of neurosteroids in modulating the strength of GABAAR-mediated inhibition, our data suggest that alcohol-induced impairments in GABAergic neurotransmission might be profoundly impacted by reduced neurosteroid biosynthesis most likely via DNA hypermethylation.
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