Evidence map›Paper›PMID 26842245›Full record

ArticleAlcoholism, clinical and experimental research2016

Role of Growth Arrest and DNA Damage-Inducible, Beta in Alcohol-Drinking Behaviors.

David P Gavin, Handojo Kusumo, Huaibo Zhang, Alessandro Guidotti, Subhash C Pandey

Abstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
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  11. Article
  12. Correlation between Oxidative Stress, Nutrition, and Cancer Initiation.International journal of molecular sciences · 2017
    Review
  13. DNA modifications in models of alcohol use disorders.Alcohol (Fayetteville, N.Y.) · 2017
    Review
  14. Article
  15. Review
  16. Emerging Role of Epigenetic Mechanisms in Alcohol Addiction.Alcoholism, clinical and experimental research · 2017
    Review
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

David P GavinJesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Handojo KusumoJesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Huaibo ZhangJesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Alessandro GuidottiCenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.
Subhash C PandeyJesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
Jesse Brown VA Medical Center · USUniversity of Illinois Chicago · US

Funding

Pilot Project Program P50AA022538 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI DENNIS R GRAYSON · 2015 to 2026
$21.3M
Signaling Mechanisms in Alcohol Drinking BehaviorsR01AA010005 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C. · 2001 to 2017
$3.0M
Nicotinic receptor stimulation and epigenetic regulation of GABAergic function.R01MH093348 · NIMH · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GUIDOTTI, ALESSANDRO · 2011 to 2015
$1.9M
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
SEROTONERGIC MECHANISMS IN ALCOHOL DEPENDENCER29AA010005 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C · 1997 to 2000
$90k
DNA Methylation in Ethanol Drinking BehaviorIK2BX001650 · VA · JESSE BROWN VA MEDICAL CENTER · PI GAVIN, DAVID P · 2013 to 2017
–
Cellular Signaling in AlcoholismI01BX000143 · VA · JESSE BROWN VA MEDICAL CENTER · PI PANDEY, SUBHASH C. · 2011 to 2014
–
BLRD VA I01 BX000143BLRD VA IK2 BX001650NIAAA NIH HHS AA-010005NIAAA NIH HHS AA-0212662NIAAA NIH HHS AA022538NIAAA NIH HHS P50 AA022538NIAAA NIH HHS R01 AA010005NIAAA NIH HHS R01 AA021662NIAAA NIH HHS R29 AA010005NIMH NIH HHS R01 MH093348
6 · The paper itself

Abstract

backgroundThe contribution of epigenetic factors, such as histone acetylation and DNA methylation, to the regulation of alcohol-drinking behavior has been increasingly recognized over the last several years. GADD45b is a protein demonstrated to be involved in DNA demethylation at neurotrophic factor gene promoters, including at brain-derived neurotrophic factor (Bdnf) which has been highly implicated in alcohol-drinking behavior.

methodsDNA methyltransferase-1 (Dnmt1), 3a, and 3b, and Gadd45a, b, and g mRNA were measured in the nucleus accumbens (NAc) and ventral tegmental areas of high ethanol (EtOH) consuming C57BL/6J (C57) and low alcohol consuming DBA/2J (DBA) mice using quantitative reverse transcriptase polymerase chain reaction (PCR). In the NAc, GADD45b protein was measured via immunohistochemistry and Bdnf9a mRNA using in situ PCR. Bdnf9a promoter histone H3 acetylated at lysines 9 and 14 (H3K9,K14ac) was measured using chromatin immunoprecipitation, and 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) using methylated DNA immunoprecipitation. Alcohol-drinking behavior was evaluated in Gadd45b haplodeficient (+/-) and null mice (-/-) utilizing drinking-in-the-dark (DID) and 2-bottle free-choice paradigms.

resultsC57 mice had lower levels of Gadd45b and g mRNA and GADD45b protein in the NAc relative to the DBA strain. C57 mice had lower NAc shell Bdnf9a mRNA levels, Bdnf9a promoter H3K9,K14ac, and higher Bdnf9a promoter 5HMC and 5MC. Acute EtOH increased GADD45b protein, Bdnf9a mRNA, and histone acetylation and decreased 5HMC in C57 mice. Gadd45b +/- mice displayed higher drinking behavior relative to wild-type littermates in both DID and 2-bottle free-choice paradigms.

conclusionsThese data indicate the importance of the DNA demethylation pathway and its interactions with histone posttranslational modifications in alcohol-drinking behavior. Further, we suggest that lower DNA demethylation protein GADD45b levels may affect Bdnf expression possibly leading to altered alcohol-drinking behavior.

Indexed as

Alcohol DrinkingAnimalsAntigens, DifferentiationBrain-Derived Neurotrophic FactorEpigenesis, GeneticGADD45 ProteinsMaleMiceMice, Inbred C57BLMice, Inbred DBAMice, KnockoutNucleus AccumbensReverse Transcriptase Polymerase Chain ReactionAntigens, DifferentiationBrain-Derived Neurotrophic FactorGadd45b protein, mouseGADD45 ProteinsAlcoholismBdnfDNA MethylationGADD45bHistoneNucleus Accumbens

Identifiers

PMID26842245
PMCPMC4743544
OpenAlexW2256070777

What OpenQuestion holds

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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.