ArticleTranslational psychiatry2024
EZH2-dependent epigenetic reprogramming in the central nucleus of amygdala regulates adult anxiety in both sexes after adolescent alcohol exposure.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Glutamatergic dysfunction of astrocytes in paraventricular nucleus of thalamus contributes to adult anxiety susceptibility in adolescent ethanol exposed mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Emerging role of N6-methyladenosine (m6A) epitranscriptomic changes in adult anxiety after adolescent alcohol exposure.Neuropharmacology · 2026Article
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Dysregulation of Central-Medial Amygdala Histone Modifiers in Preclinical Models of Ethanol Exposure.Addiction biology · 2025Review
- Galactooligosaccharides Attenuate Behavioural, Haematological and Immunological Abnormalities and Influence Gut Microbiota in Rats with Amygdala Hyperactivation Induced by Electrical Stimulation.International journal of molecular sciences · 2025Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Alcohol use and anxiety disorders occur in both males and females, but despite sharing similar presentation and classical symptoms, the prevalence of alcohol use disorder (AUD) is lower in females. While anxiety is a symptom and comorbidity shared by both sexes, the common underlying mechanism that leads to AUD and the subsequent development of anxiety is still understudied. Using a rodent model of adolescent intermittent ethanol (AIE) exposure in both sexes, we investigated the epigenetic mechanism mediated by enhancer of zeste 2 (EZH2), a histone methyltransferase, in regulating both the expression of activity-regulated cytoskeleton-associated protein (Arc) and an anxiety-like phenotype in adulthood. Here, we report that EZH2 protein levels were significantly higher in PKC-δ positive GABAergic neurons in the central nucleus of amygdala (CeA) of adult male and female rats after AIE. Reducing protein and mRNA levels of EZH2 using siRNA infusion in the CeA prevented AIE-induced anxiety-like behavior, increased H3K27me3, decreased H3K27ac at the Arc synaptic activity response element (SARE) site, and restored deficits in Arc mRNA and protein expression in both male and female adult rats. Our data indicate that an EZH2-mediated epigenetic mechanism in the CeA plays an important role in regulating anxiety-like behavior and Arc expression after AIE in both male and female rats in adulthood. This study suggests that EZH2 may serve as a tractable drug target for the treatment of adult psychopathology after adolescent alcohol exposure.
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