Evidence map›Paper›PMID 34252404›Full record

ArticleNeuropharmacology2021

Alcohol drinking during early adolescence activates microglial cells and increases frontolimbic Interleukin-1 beta and Toll-like receptor 4 gene expression, with heightened sensitivity in male rats compared to females.

Andrea Silva-Gotay, Jillian Davis, Elizabeth R Tavares, Heather N Richardson

Open access · greenAbstract read
In one paragraph

Article in Neuropharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
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, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Novel neurotherapeutic targets for substance use disorders: Neuroplasticity, neuroinflammation, gasotransmitters and non-canonical organ systems.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Consequences of adolescent drug use.Translational psychiatry · 2023
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. 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

4 authors at 1 institution in 1 country.

Andrea Silva-GotayNeuroscience and Behavior Graduate Program, University of Massachusetts, Amherst, MA, 01003, USA.
Jillian DavisDepartment of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
Elizabeth R TavaresDepartment of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
Heather N RichardsonNeuroscience and Behavior Graduate Program, University of Massachusetts, Amherst, MA, 01003, USA; Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, 01003, USA. Electronic address: hrichardson@cns.umass.edu.
University of Massachusetts Amherst · US

Funding

Adolescent binge drinking and effects on adult brain and behavior: the importance of sex differencesR01AA024774 · NIAAA · UNIVERSITY OF MASSACHUSETTS AMHERST · PI RICHARDSON, HEATHER NOËL · 2016 to 2020
$1.8M
Protective effects of ovarian hormones: sex-specific differences in tlr4 expression after adolescent alcoholF99NS115272 · NINDS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI SILVA-GOTAY, ANDREA · 2019 to 2021
$89k
NIAAA NIH HHS R01 AA024774NINDS NIH HHS F99 NS115272
6 · The paper itself

Abstract

Adolescent drinking is risky because neural circuits in the frontal lobes are undergoing maturational processes important for cognitive function and behavioral control in adulthood. Previous studies have shown that myelinated axons in the medial prefrontal cortex (mPFC) are particularly sensitive to alcohol drinking, especially in males. Pro-inflammatory mediators like toll-like receptor 4 (TLR4) and interleukin-1 beta (IL1b) have been implicated in alcohol induced-inflammation and demyelination; thus, herein we test the hypothesis that voluntary alcohol drinking early in adolescence elicits a pro-inflammatory state that is more pronounced in the brain of males compared to females. Adolescent male and female Wistar rats self-administered sweetened alcohol or sweetened water from postnatal days 28-42 and separate sets of brains were processed for 1) immunolabeling for ionized calcium-binding adapter molecule 1 to analyze microglial cell morphology, or 2) qPCR analysis of gene expression of pro-inflammatory mediators. Binge drinking alcohol activated microglia in the mPFC and hippocampus of both males and females, suggesting that voluntary alcohol exposure initiates an inflammatory response. Il1b mRNA was upregulated in the mPFC of both sexes. Conversely, Tlr4 mRNA levels were elevated after drinking only in males, which could explain more robust effects of alcohol on myelin in this region in developing males compared to females. Il1b mRNA changes were not observed in the hippocampus, but alcohol elevated Tlr4 mRNA in both sexes, highlighting regional specificity in inflammatory responses to alcohol. Overall, these findings give insight into potential mechanisms by which low-to-moderate voluntary alcohol intake impacts the developing brain. This article is part of the special Issue on 'Vulnerabilities to Substance Abuse'.

Indexed as

Alcohol DrinkingAnimalsBinge DrinkingConditioning, OperantFemaleGene Expression RegulationHippocampusInterleukin-1betaLimbic SystemMaleRatsRats, WistarRNA, MessengerSelf AdministrationSex CharacteristicsToll-Like Receptor 4IL1B protein, ratInterleukin-1betaRNA, MessengerTlr4 protein, ratToll-Like Receptor 4AdolescenceAlcoholBinge drinkingCytokinesDevelopmentFemaleHippocampusIba1Il1bInterleukin-1 betaMaleMicrogliamPFCNeuroinflammationOperant self-administrationPrefrontal cortexRatsSex differencesTlr4Toll-like receptor 4

Identifiers

PMID34252404
PMCPMC8552486
OpenAlexW3180659133

What OpenQuestion holds

Textmetadata
LicenceTDM
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.