Consistent changes in global gene expression patterns despite strong variation in individual gene expression in the male mouse hippocampus following early life stress
Neurobiology of Stress, vol. 42, pp. 100808
Abstract
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.
Authors 12
-
Jeniffer Sanguino‐Gómez corresponding Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center · University of Amsterdam
Affiliation as printed
Brain Plasticity Group, SILS-CNS, University of Amsterdam, Amsterdam, the Netherlands
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
-
Jacobus C. Buurstede Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
-
Universidade de São Paulo · University of Amsterdam
Affiliation as printed
Brain Plasticity Group, SILS-CNS, University of Amsterdam, Amsterdam, the Netherlands
Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil
-
Marcia Santos da Silva Umeoka Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center
Universidade de São Paulo · Leiden University Medical Center
Affiliation as printed
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil
-
Max Gentenaar Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
-
Affiliation as printed
Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil
-
Affiliation as printed
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neurosciences-King's College London, UK
-
Oncode Institute · Princess Máxima Center
Affiliation as printed
Oncode Institute, Utrecht, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
-
University of Cologne · Erasmus MC · Oncode Institute · Princess Máxima Center · Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases · Erasmus MC Cancer Institute
Affiliation as printed
Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
Institute for Genome Stability in Ageing and Disease, Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Oncode Institute, Utrecht, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
-
Affiliation as printed
Brain Plasticity Group, SILS-CNS, University of Amsterdam, Amsterdam, the Netherlands
-
University Medical Center Groningen · University of Groningen
Affiliation as printed
University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
-
Onno Cornelis Meijer corresponding Aachen Department of Medicine Division of Endocrinology, Leiden University Medical Center
Leiden University Medical Center
Affiliation as printed
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
Cited by 0 stored of 0
No patents citing this paper on Lens.org (checked 2026-10-11).