Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress.

Overview

Authors: Polina Ritter¹, Anastasiia Shuliupova¹, Vasiliy Reshetnikov^1,2, Natalia Bondar¹

ORCID iDs: Polina Ritter, Vasiliy Reshetnikov, Natalia Bondar

Institute of Cytology and Genetics (ICG), Siberian Branch of Russian Academy of Sciences (SB RAS), Prospekt Akad. Lavrentyeva 10, 630090 Novosibirsk, Russia; (P.R.)
Translational Medicine Research Center, Sirius University of Science and Technology, Sirius Federal Territory, 354340 Sochi, Russia

Institutions: Institute of Cytology and Genetics (Russia); Siberian Branch of the Russian Academy of Sciences (Russia); Sirius University of Science and Technology (Russia)

Journal: International journal of molecular sciences, volume 27, issue 14, article 6442

Dates: received 18 June 2026; accepted 19 July 2026; published online 20 July 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.3390/ijms27146442 · PMID 42511784 · PMCID PMC13410218 · OpenAlex W7169817649

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: genetics / omics (modality), mouse (organism)

Methods: Statistics, Machine learning

Keywords: chronic stress, HPA axis, dexamethasone, glucocorticoid signaling, RNA-seq, prefrontal cortex, dorsal raphe nucleus, stress resilience

MeSH: Dorsal Raphe Nucleus*, Glucocorticoids*, Prefrontal Cortex*, Signal Transduction*, Stress, Psychological*, Transcriptome*, Animals, Coping Skills, Dexamethasone, Gene Expression Profiling, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, Phenotype, Receptors, Glucocorticoid, Social Defeat (* major topic)

Topic: Stress Responses and Cortisol (Behavioral Neuroscience, Neuroscience), according to OpenAlex

Funding: Russian Science Foundation (24-15-00301)

Citations: not cited yet (Europe PMC); 61 references in the paper

Abstract

Chronic stress produces marked individual differences in behavioral adaptation and glucocorticoid sensitivity, but the molecular basis of this variability remains poorly understood. Here, we examined transcriptional responses to glucocorticoid receptor activation after chronic social defeat stress (CSDS) in male C57BL/6J mice. Based on behavioral responses during social interaction, stressed animals were classified into active coping strategy (AS) and passive coping strategy (PS) phenotypes. A total of 24 h after the final stress session, mice received 2 µg/g of dexamethasone (DEX) or a saline injection, and transcriptomic profiling of the prefrontal cortex (PFC) and dorsal raphe nucleus (DRN) was performed 6 h later using RNA sequencing. Chronic stress induced pronounced phenotype- and region-specific transcriptional alterations. The PFC showed extensive stress-associated gene expression changes, particularly in PS animals, whereas the DRN displayed comparatively fewer differentially expressed genes. Functional enrichment analysis nevertheless revealed substantial pathway-level remodeling in both regions. PS animals exhibited extensive pathway reorganization in the DRN, while AS animals showed broader suppression of enriched biological pathways in the PFC. Acute DEX administration further revealed marked phenotype-dependent differences in glucocorticoid-responsive transcriptional programs, with the strongest response observed in AS animals. Together, these findings demonstrate that chronic stress establishes distinct transcriptional states that shape subsequent DEX-induced transcriptional responses in a phenotype- and brain region-specific manner. Our results provide new insight into the molecular mechanisms underlying heterogeneity in stress adaptation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

geo:GSE330674, at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

Raw and processed RNA-seq data generated in this study have been deposited in the Gene Expression Omnibus (GEO) under accession numbers GSE330674 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330674) (BioProject PRJNA846517) and GSE330675 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330675) (BioProject PRJNA1433139).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 8 keywords, 17 MeSH terms, 1 funder, 59 references.

Cite

This paper

Ritter, P., Shuliupova, A., Reshetnikov, V., & Bondar, N. (2026). Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress. International journal of molecular sciences, 27(14), 6442. https://doi.org/10.3390/ijms27146442

BibTeX

@article{ritter2026phenotype, author = {Ritter, Polina and Shuliupova, Anastasiia and Reshetnikov, Vasiliy and Bondar, Natalia}, title = {{Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress}}, journal = {International journal of molecular sciences}, year = {2026}, month = jul, volume = {27}, number = {14}, pages = {6442}, publisher = {Multidisciplinary Digital Publishing Institute (MDPI)}, issn = {1422-0067}, doi = {10.3390/ijms27146442}, url = {https://doi.org/10.3390/ijms27146442}, pmid = {42511784}, pmcid = {PMC13410218} }

RIS

TY - JOUR AU - Ritter, Polina AU - Shuliupova, Anastasiia AU - Reshetnikov, Vasiliy AU - Bondar, Natalia TI - Phenotype-Specific Transcriptomic Responses to Glucocorticoid Signaling in the Prefrontal Cortex and Dorsal Raphe Nucleus Following Chronic Social Stress T2 - International journal of molecular sciences J2 - Int J Mol Sci PY - 2026 DA - 2026/07/20 VL - 27 IS - 14 SP - 6442 SN - 1422-0067 PB - Multidisciplinary Digital Publishing Institute (MDPI) DO - 10.3390/ijms27146442 UR - https://doi.org/10.3390/ijms27146442 LA - en ER -

CSL-JSON

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