ArticleTranslational psychiatry2021
Transcriptomics identifies STAT3 as a key regulator of hippocampal gene expression and anhedonia during withdrawal from chronic alcohol exposure.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Pathway-Level Synthesis Reveals Contrast-Dependent Rat Brain Transcriptomic Responses to Alcohol.International journal of molecular sciences · 2026Article
- Heroin addiction modulates transcription factor binding in regulatory regions of the human putamen.Scientific reports · 2026Article
- Epigenetic and Transcriptomic Impacts of Ethanol Vary by Brain Region and Extent of Exposure.eNeuro · 2026Article
- Not just neurons: glial mechanisms driving sex-specific vulnerability to withdrawal and relapse in substance use disorder.Frontiers in neuroendocrinology · 2026Review
- Astrocytes and Alcohol Throughout the Lifespan.Biological psychiatry · 2026Review
- A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co-expression network module eigengenes.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2025Article
- Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.Science (New York, N.Y.) · 2024Article
- Transcriptional Dysregulation of Cholesterol Synthesis Underlies Hyposensitivity to GABA in the Ventral Tegmental Area During Acute Alcohol Withdrawal.Biological psychiatry · 2024Article
- Effects of repeated alcohol abstinence on within-subject prefrontal cortical gene expression in rhesus macaques.Advances in drug and alcohol research · 2024Article
- Alcohol, HMGB1, and Innate Immune Signaling in the Brain.Alcohol research : current reviews · 2024Review
- Conserved role for PCBP1 in altered RNA splicing in the hippocampus after chronic alcohol exposure.Molecular psychiatry · 2023Article
- Article
- Neuroimmune interactions with binge alcohol drinking in the cerebellum of IL-6 transgenic mice.Neuropharmacology · 2023Article
- The relationship between self-control and mental health problems among Chinese university students.Frontiers in public health · 2023Article
- Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction.Frontiers in psychiatry · 2023Article
- Article
- Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking.International journal of molecular sciences · 2022Article
- Chronic ethanol consumption exacerbates future stress-enhanced fear learning, an effect mediated by dorsal hippocampal astrocytes.Alcoholism, clinical and experimental research · 2022Article
- Multi-omics signatures of alcohol use disorder in the dorsal and ventral striatum.Translational psychiatry · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Alcohol use disorder (AUD) is highly comorbid with depression. Withdrawal from chronic alcohol drinking results in depression and understanding brain molecular mechanisms that drive withdrawal-related depression is important for finding new drug targets to treat these comorbid conditions. Here, we performed RNA sequencing of the rat hippocampus during withdrawal from chronic alcohol drinking to discover key signaling pathways involved in alcohol withdrawal-related depressive-like behavior. Data were analyzed by weighted gene co-expression network analysis to identify several modules of co-expressed genes that could have a common underlying regulatory mechanism. One of the hub, or highly interconnected, genes in module 1 that increased during alcohol withdrawal was the transcription factor, signal transducer and activator of transcription 3 (Stat3), a known regulator of immune gene expression. Total and phosphorylated (p)STAT3 protein levels were also increased in the hippocampus during withdrawal after chronic alcohol exposure. Further, pSTAT3 binding was enriched at the module 1 genes Gfap, Tnfrsf1a, and Socs3 during alcohol withdrawal. Notably, pSTAT3 and its target genes were elevated in the postmortem hippocampus of human subjects with AUD when compared with control subjects. To determine the behavioral relevance of STAT3 activation during alcohol withdrawal, we treated rats with the STAT3 inhibitor stattic and tested for sucrose preference as a measure of anhedonia. STAT3 inhibition alleviated alcohol withdrawal-induced anhedonia. These results demonstrate activation of STAT3 signaling in the hippocampus during alcohol withdrawal in rats and in human AUD subjects, and suggest that STAT3 could be a therapeutic target for reducing comorbid AUD and depression.
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