Evidence map›Paper›PMID 34839533›Full record

ArticleAlcoholism, clinical and experimental research2022

Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.

James W Bogenpohl, Rory M Weston, Taylor N Foreman, Kaitlyn E Kitchen, Michael F Miles

Open access · greenAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 54% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Intracellular Chloride Channels: A Rising Target in Lung Disease Research.Journal of respiratory biology and translational medicine · 2025
    Article
  4. 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

5 authors at 2 institutions in 1 country.

James W BogenpohlDepartment of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia, USA.ORCID 0000-0001-7214-3404
Rory M WestonDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Taylor N ForemanDepartment of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia, USA.
Kaitlyn E KitchenDepartment of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia, USA.
Michael F MilesDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
Christopher Newport University · USVirginia Commonwealth University · US

Funding

Project 5 - Genetic architecture of alcohol use disorder using cross-trait genetic correlations and public next-generation sequencing studiesP50AA022537 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI Brien P Riley · 2014 to 2026
$19.6M
Gsk3b in ethanol consumption and as a therapeutic target for alcohol use disorderR01AA027581 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI MILES, MICHAEL F · 2019 to 2023
$1.7M
Cross-species genetic analysis of ethanol-related behaviorR01AA020634 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI GROTEWIEL, MICHAEL S., MILES, MICHAEL F · 2012 to 2016
$1.3M
The Role and Mechanisms of Clic4 in Modifying Ethanol-Related BehaviorsF30AA026497 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI WESTON, RORY MICHAEL · 2017 to 2021
$178k
NIAAA NIH HHS F30 AA026497NIAAA NIH HHS P50 AA022537NIAAA NIH HHS R01 AA020634NIAAA NIH HHS R01 AA027581
6 · The paper itself

Abstract

backgroundChloride intracellular channel 4 (CLIC4) is a multifunctional metamorphic protein for which a growing body of evidence supports a major role in the brain's molecular and behavioral responses to ethanol (EtOH). Although key to understanding the functional biology underlying this role, little is known about the cellular and subcellular expression patterns of CLIC4 in brain and how they are affected by EtOH.

methodsWe used qRT-PCR to assess Clic4 mRNA expression in the medial prefrontal cortex (mPFC) of C57BL/6J mice in the absence and presence of acute EtOH exposure. Two complementary immunohistochemical techniques were employed to assess the subcellular localization of the CLIC4 protein and its pattern of expression across brain cell types in the mPFC in the absence and presence of acute EtOH.

resultsThrough immunohistochemical and stereological techniques, we show that CLIC4 protein is robustly expressed by oligodendrocytes (most abundant), microglia, and astrocytes, with minimal expression in neurons. Following acute EtOH exposure, we observed a rapid increase in Clic4 mRNA expression in female but not male mice and an overall increase in the number of oligodendrocytes and astrocytes expressing the CLIC4 protein.

conclusionsThese findings suggest that Clic4 functions as an early response gene for acute EtOH in brain, which likely underlies its ability to modulate EtOH behavior. Our results also suggest that the role of CLIC4 in the brain's response to EtOH is mediated through oligodendrocytes.

Indexed as

AnimalsAstrocytesBehavior, AnimalChloride ChannelsEthanolFemaleGene Expression RegulationMaleMiceMice, Inbred C57BLMitochondrial ProteinsOligodendrogliaPrefrontal CortexRNA, MessengerSex CharacteristicsTranscriptomeChloride ChannelsCLIC protein, mouseEthanolMitochondrial ProteinsRNA, MessengerCLIC4EtOHimmunohistochemistrymiceqRT-PCR

Identifiers

PMID34839533
PMCPMC8799520
OpenAlexW3215263249

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.