Evidence map›Paper›PMID 39369762›Full record

ArticleBiological psychiatry2025

Astrocytic CREB in Nucleus Accumbens Promotes Susceptibility to Chronic Stress.

Leanne M Holt, Trevonn M Gyles, Eric M Parise, Angelica M Minier-Toribio, Matthew Rivera, Tamara Markovic, Szu-Ying Yeh, Eric J Nestler

Abstract read
In one paragraph

Article in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
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  9. How dopamine guides our social world.Pharmacological reviews · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Leanne M HoltNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Trevonn M GylesNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Eric M PariseNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Angelica M Minier-ToribioNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Matthew RiveraNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Tamara MarkovicNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Szu-Ying YehNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Eric J NestlerNash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: eric.nestler@mssm.edu.

Funding

Using neuroeconomics to disentangle the transcriptional mechanisms underlying resilience versus susceptibility to stressR01MH051399 · NIMH · YALE UNIVERSITY · PI NESTLER, ERIC J. · 1994 to 2023
$10.2M
RESEARCH TRAINING - BIOLOGICAL SCIENCEST32MH014276 · NIMH · YALE UNIVERSITY · PI Marina R Picciotto · 1985 to 2026
$7.2M
Glial-mediated synaptic remodeling in drug addictionR01DA040620 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yan Dong, ERIC J. NESTLER · 2016 to 2026
$5.3M
Cocaine-induced adaptation in NMDA receptorsR37DA023206 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yan Dong · 2018 to 2026
$3.9M
Cocaine-induced Adaptation in NMDA Receptors in Nucleus AccumbensR01DA023206 · NIDA · WASHINGTON STATE UNIVERSITY · PI DONG, YAN · 2008 to 2017
$3.0M
Epigenetic Mechanisms of Chronic Stress ActionR01MH129306 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ERIC J. NESTLER · 2023 to 2026
$2.7M
Training Program in Substance Use DisordersT32DA053558 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Paul J. Kenny · 2021 to 2026
$2.6M
Cellular and Behavioral Function of Astrocytic Dopamine SignalingR01DA060868 · NIDA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yan Dong · 2024 to 2026
$1.3M
NIDA NIH HHS R01 DA023206NIDA NIH HHS R01 DA040620NIDA NIH HHS R01 DA060868NIDA NIH HHS R37 DA023206NIDA NIH HHS T32 DA053558NIMH NIH HHS R01 MH051399NIMH NIH HHS R01 MH129306NIMH NIH HHS T32 MH014276
6 · The paper itself

Abstract

backgroundIncreasing evidence implicates astrocytes in stress and depression in both rodent models and human major depressive disorder. Despite this, little is known about the transcriptional responses to stress of astrocytes within the nucleus accumbens (NAc), a key brain reward region, and their influence on behavioral outcomes.

methodsWe used whole-cell sorting, RNA sequencing, and bioinformatic analyses to investigate the NAc astrocyte transcriptome in male mice in response to chronic social defeat stress (CSDS). Immunohistochemistry was used to determine stress-induced changes in astrocytic CREB (cAMP response element binding protein) within the NAc. Finally, astrocytic regulation of depression-like behavior was investigated using viral-mediated manipulation of CREB in combination with CSDS.

resultsWe found a robust transcriptional response in NAc astrocytes to CSDS in stressed mice, with changes seen in both stress-susceptible and stress-resilient animals. Bioinformatic analysis revealed CREB, a transcription factor widely studied in neurons, as one of the top-predicted upstream regulators of the NAc astrocyte transcriptome, with opposite activation states implicated in resilient versus susceptible mice. This bioinformatic deduction was confirmed at the protein level with immunohistochemistry. Moreover, NAc astrocyte morphological complexity correlated with CREB activation and was reduced selectively in astrocytes of resilient mice. Viral overexpression of CREB selectively in NAc astrocytes promoted susceptibility to chronic stress.

conclusionsTogether, our data demonstrate that the astrocyte transcriptome responds robustly to CSDS and that transcriptional regulation in astrocytes contributes to depressive-like behaviors. A better understanding of transcriptional regulation in astrocytes may reveal unknown molecular mechanisms underlying neuropsychiatric disorders.

Indexed as

AstrocytesCyclic AMP Response Element-Binding ProteinNucleus AccumbensStress, PsychologicalAnimalsBehavior, AnimalDisease Models, AnimalMaleMiceMice, Inbred C57BLSocial DefeatTranscriptomeCyclic AMP Response Element-Binding ProteinAstrocytesCREBDepressionNucleus accumbensRNA sequencingStress

Identifiers

PMID39369762
PMCPMC11971392

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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.