Evidence map›Paper›PMID 30827484›Full record

ArticleBiological psychiatry2019

Adolescent Alcohol Exposure Epigenetically Suppresses Amygdala Arc Enhancer RNA Expression to Confer Adult Anxiety Susceptibility.

Evan J Kyzar, Huaibo Zhang, Subhash C Pandey

Open access · greenAbstract read
In one paragraph

Article in Biological psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 80 citations in OpenAlex.

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  17. Consequences of adolescent drug use.Translational psychiatry · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Evan J KyzarCenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Huaibo ZhangCenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Subhash C PandeyCenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois; Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois. Electronic address: scpandey@uic.edu.
Jesse Brown VA Medical Center · USUniversity of Illinois Chicago · US

Funding

Pilot Project Program P50AA022538 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Elizabeth J Glover · 2015 to 2026
$21.3M
Role of AIE in Epigenetic and Behavioral Changes at AdulthoodU01AA019971 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C. · 2010 to 2024
$5.6M
2/2 NADIA U24 Epigenetic/Molecular CoreU24AA024605 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C. · 2015 to 2024
$3.6M
Signaling Mechanisms in Alcohol Drinking BehaviorsR01AA010005 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C. · 2001 to 2017
$3.0M
Role of the CB1 receptor signaling in alcohol consumptionR01AA021662 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C., YARAGUDRI, VINOD K · 2014 to 2017
$1.4M
Brain histone methylation mechanisms in adulthood after adolescent alcohol exposureF30AA024948 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KYZAR, EVAN · 2016 to 2019
$197k
NIAAA NIH HHS F30 AA024948NIAAA NIH HHS P50 AA022538NIAAA NIH HHS R01 AA010005NIAAA NIH HHS R01 AA021662NIAAA NIH HHS U01 AA019971NIAAA NIH HHS U24 AA024605
6 · The paper itself

Abstract

backgroundAdolescent intermittent ethanol (AIE) exposure is an emerging risk factor for adult psychopathology, such as anxiety disorders. Enhancer RNAs (eRNAs) are short noncoding RNAs transcribed from enhancer regions that regulate synaptic plasticity-associated gene expression, including Arc, but their role in AIE-induced susceptibility to anxiety in adulthood is unknown.

methodsRats were exposed to AIE (ethanol exposure 2 days on/off) or intermittent normal saline during postnatal days 28 to 41 and allowed to grow to adulthood for analysis of behavior and biochemical measures. Some AIE rats and rats with intermittent normal saline exposure were exposed to an acute challenge with ethanol in adulthood. Cohorts of alcohol-naïve adult rats were cannulated in the central nucleus of amygdala and infused with either Kdm6b small interfering RNA or an antisense locked nucleic acid oligonucleotide specific to Arc eRNA before behavioral and biochemical analysis.

resultsAIE adult rats displayed heightened anxiety and decreased Arc eRNA expression, which is regulated epigenetically through decreased Kdm6b expression. This triggered condensed chromatin at the synaptic activity response element site and promoter of the Arc gene, facilitating increased negative elongation factor binding to the Arc promoter and decreasing Arc expression in the amygdala. Knockdown of Kdm6b or Arc eRNA expression in the central nucleus of amygdala provoked anxiety in alcohol-naïve adult rats and recapitulated the molecular and epigenetic phenotypes of AIE.

conclusionsThese data suggest that eRNA regulation via epigenetic reprogramming in the amygdala, particularly at the Arc synaptic activity response element site, contributes to adult anxiety after adolescent alcohol exposure.

Indexed as

Age FactorsAmygdalaAnimalsAnxietyCytoskeletal ProteinsEnhancer Elements, GeneticEpigenesis, GeneticJumonji Domain-Containing Histone DemethylasesMaleMicroinjectionsNerve Tissue ProteinsOligonucleotides, AntisenseRatsRNA, Small InterferingRNA, Small Untranslatedactivity regulated cytoskeletal-associated proteinCytoskeletal ProteinsJumonji Domain-Containing Histone DemethylasesKdm6b protein, ratNerve Tissue ProteinsOligonucleotides, AntisenseRNA, Small InterferingRNA, Small UntranslatedAdolescent alcoholAmygdalaAnxietyArcEnhancer RNAepigenetic

Identifiers

PMID30827484
PMCPMC6684056
OpenAlexW2910936809

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.