Evidence map›Paper›PMID 40659615›Full record

ArticleNature communications2025

Paradoxical mTORC1-Dependent microRNA-mediated Translation Repression in the Nucleus Accumbens of Male Mice Consuming Alcohol Attenuates Glycolysis.

Yann Ehinger, Sophie Laguesse, Khanhky Phamluong, Alexandra Salvi, Yoshitaka J Sei, Zachary W Hoisington, Drishti Soneja, Sowmya Gunasekaran, Ken Nakamura, Dorit Ron

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Yann EhingerDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.ORCID http://orcid.org/0000-0001-9314-6575
Sophie LaguesseDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Khanhky PhamluongDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Alexandra SalviDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.ORCID http://orcid.org/0000-0002-0148-2406
Yoshitaka J SeiGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California, USA.
Zachary W HoisingtonDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Drishti SonejaDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.ORCID http://orcid.org/0000-0002-0137-0906
Sowmya GunasekaranDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.
Ken NakamuraDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA.ORCID http://orcid.org/0000-0002-9192-182X
Dorit RonDepartment of Neurology, University of California, San Francisco, San Francisco, California, USA. dorit.ron@ucsf.edu.ORCID http://orcid.org/0000-0001-5161-967X

Funding

Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human CellsR01AG065428 · NIA · J. DAVID GLADSTONE INSTITUTES · PI NAKAMURA, KEN · 2020 to 2024
$3.7M
Understand and probing disrupted glucose metabolism in Alzheimer's diseaseRF1AG064170 · NIA · J. DAVID GLADSTONE INSTITUTES · PI CHAUMEIL, MYRIAM MARIANNE, NAKAMURA, KEN · 2019 to 2019
$3.6M
mTOR Signaling and Alcohol Use DisorderR01AA027474 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RON, DORIT · 2018 to 2022
$1.6M
Understanding how neuronal glucose metabolism changes in AD due to ApoE4F32AG082460 · NIA · J. DAVID GLADSTONE INSTITUTES · PI SEI, YOSHI · 2023 to 2025
$240k
NIAAA NIH HHS R01 AA027474NIA NIH HHS F32 AG082460NIA NIH HHS R01 AG065428NIA NIH HHS RF1 AG064170
6 · The paper itself

Abstract

mTORC1 promotes protein translation, learning and memory, and neuroadaptations that underlie alcohol use disorder (AUD). The mechanisms underlying alcohol-mediated mTORC1-dependent neuroadaptations that drive AUD are not well understood. We report that activation of mTORC1 in the nucleus accumbens (NAc) D1 neurons of male mice consuming alcohol results in paradoxical mTORC1-dependent repression of translation of transcripts, including Aldolase A, an essential enzyme in glycolysis. We further show that mTORC1-dependent Aldolase A translation repression in D1 neurons is mediated through upregulation of miR-34a-5p expression. Alcohol-mediated mTORC1 repression of Aldolase A translation in D1 neurons inhibits glycolysis in the NAc. Finally, we report that overexpression of miR-34a-5p in D1 NAc neurons increases, whereas systemic administration of L-lactate, the final product of glycolysis, attenuates excessive alcohol intake. Our data suggest that alcohol promotes paradoxical actions of mTORC1 on translation and glycolysis which in turn drive excessive alcohol use.

Indexed as

Alcohol DrinkingEthanolGlycolysisMechanistic Target of Rapamycin Complex 1MicroRNAsNucleus AccumbensProtein BiosynthesisAlcoholismAnimalsFructose-Bisphosphate AldolaseLactic AcidMaleMiceMice, Inbred C57BLNeuronsEthanolFructose-Bisphosphate AldolaseLactic AcidMechanistic Target of Rapamycin Complex 1MicroRNAsMIRN34a microRNA, mouse

Identifiers

PMID40659615
PMCPMC12259992

What OpenQuestion holds

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Registered trials

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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.