Evidence map›Paper›PMID 26357588›Full record

ArticleBrain and behavior2015

Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons.

Rola A Bekdash, Neil L Harrison

Open access · goldAbstract read
In one paragraph

Article in Brain and behavior, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Regulation of GABAInternational journal of molecular sciences · 2020
    Review
  5. Article
  6. Sex Differences in the Expression of the α5 Subunit of the GABAAlcoholism, clinical and experimental research · 2020
    Article
  7. MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  8. Article
  9. Role of GABAMolecular brain · 2017
    Review
  10. Emerging roles for ncRNAs in alcohol use disorders.Alcohol (Fayetteville, N.Y.) · 2017
    Review
  11. Article
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

2 authors at 1 institution in 1 country.

Rola A BekdashDepartment of Anesthesiology, Columbia University New York, New York, 10032.
Neil L HarrisonDepartment of Anesthesiology, Columbia University New York, New York, 10032 ; Department of Pharmacology, Columbia University New York, New York, 10032.
Columbia University · US

Funding

ANESTHESIOLOGY RESEARCH TRAININGT32GM008464 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI CHARLES W EMALA, May Hua · 1992 to 2026
$6.0M
Alcohol and Dopamine Release: Cellular and Synaptic MechanismsR01AA019801 · NIAAA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HARRISON, NEIL L., SULZER, DAVID · 2010 to 2014
$1.8M
Alcohol withdrawal and tonic inhibition in the thalamus.F32AA022545 · NIAAA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BEKDASH, ROLA · 2013 to 2014
$95k
NIAAA NIH HHS AA19801NIAAA NIH HHS F32 AA022545-01A1NIGMS NIH HHS T32 GM008464NIGMS NIH HHS T32 GM08464
6 · The paper itself

Abstract

backgroundAlcohol abuse and dependence are a serious public health problem. A large number of alcohol-regulated genes, (ARGs) are known to be influenced by alcohol use and withdrawal (AW), and recent evidence suggests that neuroadaptation to alcohol may be due in part to epigenetic changes in the expression of ARGs. Gabra4, which encodes the α4 subunit of GABAA receptors (GABAARs), is one of a number of ARGs that show remarkable plasticity in response to alcohol, being rapidly upregulated by acute alcohol exposure. This study addressed the effects of AW on changes in the expression of Gabra4 and related genes that encode other subunits of GABAARs, and the potential regulation of Gabra4 by microRNAs.

methodsWe studied gene and microRNAs expression, using RT-PCR and microRNA microarray in cultured cortical neurons treated with alcohol, which was then removed in order to simulate AW in vitro. We also used microRNA mimics or inhibitors, and a promoter-reporter construct carrying the 3'UTR of Gabra4.

resultsEleven hours after removal of alcohol, Gabra4 was downregulated, with a modest increase in the expression of Gabrg2, but no change in the expression of Gabra1, Gabrd, or Gabrb2. microRNA profiling in neurons undergoing AW revealed upregulation in the expression of miR-155, miR-186, miR-24, and miR-375 after 8 h of AW. Transfection with molecular mimics of miR-186, miR-24, or miR-375 also downregulated Gabra4 expression, whereas transfection with the corresponding inhibitors of these microRNAs normalized Gabra4 expression in AW neurons to the level measured in control neurons. Promoter-reporter experiments supported the idea that miR-155, miR-186, miR-24, miR-27b, or miR-375 bind to the 3'UTR of Gabra4 and thereby inhibit protein production.

conclusionsOur data suggest that AW decreases Gabra4 expression, and that this may be mediated in part by the induction of specific microRNAs in cortical neurons during AW.

Indexed as

AnimalsCells, CulturedCerebral CortexDown-RegulationEthanolMaleMiceMice, Inbred C57BLMicroRNAsNeuronsReceptors, GABA-ASubstance Withdrawal SyndromeEthanolGabra4 protein, mouseMicroRNAsReceptors, GABA-AAlcohol withdrawalcortexdownregulationGabra4microRNA

Identifiers

PMID26357588
PMCPMC4559018
OpenAlexW2160284898

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.