Consistent changes in global gene expression patterns despite strong variation in individual gene expression in the male mouse hippocampus following early life stress
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Le résumé fourni par la source
Exposure to excessive and/or chronic stressors during early life is a well-established risk factor for later life stress-related mood disorders. Glucocorticoids are often implied as mediators of the long-term effects of early life stress (ELS), given their powerful transcriptional effects via the glucocorticoid receptor (GR). Previous work in rodents showed that the GR-antagonist RU486 administered during early puberty can reverse some of the behavioral and cellular effects of ELS. Here, we investigated the long-term transcriptional effects of ELS, using the limited bedding and nesting model, on the hippocampus of adult or adolescent male mice. The effects on the adult dorsal hippocampal transcriptome, established in two separate cohorts (of two labs), were found to be inconsistent. The same inconsistency was observed when investigating the transcriptome in adolescent mice - thus examining the tissue with a shorter interval after ELS - in tissue from two cohorts where virtually all sources of variation were controlled for, involving the same ELS protocol, laboratory, and experimenter. Interestingly, despite the limited overlap of individual differentially expressed genes between cohorts, we did observe a consistent pattern at a more global transcriptional level: a preferential upregulation of shorter genes and progressive downregulation with increasing gene length (as a continuous variable) after ELS, consistent with a gene-length-dependent transcription decline (GLTD) pattern. This GLTD pattern was accompanied by an enrichment of aging-associated transcriptomic changes in glial and vascular brain cell types during adolescence, a signature that was attenuated in adulthood. Together, these findings indicate that while individual gene-level responses to ELS are highly variable, robust and reproducible transcriptional patterns emerge at the level of global gene architecture (based on length) and cellular aging signatures.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Consistent changes in global gene expression patterns despite strong variation in individual gene expression in the male mouse hippocampus following early life stress
- Date Crossref
- 01/06/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Netherlands Institute for Neuroscience pays non établi dans la noticeStructure de recherche
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Leiden University Medical Center Department of Medicine pays non établi dans la noticeOrganisme public
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Universidade de São Paulo pays non établi dans la noticeUniversité ou école supérieure
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King's College London Department of Psychological Medicine pays non établi dans la noticeUniversité ou école supérieure
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Oncode Institute pays non établi dans la noticeUniversité ou école supérieure
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Princess Máxima Center pays non établi dans la noticeÉtablissement de santé
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Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases pays non établi dans la noticeStructure de recherche
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Erasmus MC Cancer Institute pays non établi dans la noticeÉtablissement de santé
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University Medical Center Groningen pays non établi dans la noticeÉtablissement de santé
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University of Groningen pays non établi dans la noticeUniversité ou école supérieure
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University of Amsterdam SILS-CNS pays non établi dans la noticeUniversité ou école supérieure
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Ribeirão Preto School of Medicine pays non établi dans la noticeUniversité ou école supérieure
Netherlands Institute for Neuroscience, Department of Medicine — Leiden University Medical Center et Universidade de São Paulo, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.