Prenatal adversity configures the transcriptome of a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety
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PROVIDER: PRJNA1198975 | ENA |
REPOSITORIES: ENA
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Project description:Prenatal adversity configures the transcriptome of a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety
| PRJNA1199323 | ENA
Project description:Adverse prenatal environment is a risk factor for the development of psychiatric disorders. Although studies have implicated epigenetic mechanisms, little is known about how epigenomic changes come about and lead to abnormal behaviors in affected individuals. We sought to identify epigenomic and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to avoidance of threatening contexts, that persist and promote anxiety-like behavior in mice. Here we show that adversity shifted the methylation of enhancers and promoters with intermediate methylation and altered synapse-related gene expression, resulting in epigenetic and transcriptional heterogeneity in the vDG. Exposure to an anxiogenic environment recruited vDG neurons with the most transcriptional impact. Differentially expressed synapse-relevant genes in ensemble neurons tended to be differentially methylated. Finally, this ensemble exhibited higher activity in threatening than safe environment suggesting a prenatal adversity-induced epigenetic and neurobiological sequalae that leads to anxiety.
2025-07-31 | GSE284416 | GEO
Project description:Adverse prenatal environment is a risk factor for the development of psychiatric disorders. Although studies have implicated epigenetic mechanisms, little is known about how epigenomic changes come about and lead to abnormal behaviors in affected individuals. We sought to identify epigenomic and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to avoidance of threatening contexts, that persist and promote anxiety-like behavior in mice. Here we show that adversity shifted the methylation of enhancers and promoters with intermediate methylation and altered synapse-related gene expression, resulting in epigenetic and transcriptional heterogeneity in the vDG. Exposure to an anxiogenic environment recruited vDG neurons with the most transcriptional impact. Differentially expressed synapse-relevant genes in ensemble neurons tended to be differentially methylated. Finally, this ensemble exhibited higher activity in threatening than safe environment suggesting a prenatal adversity-induced epigenetic and neurobiological sequalae that leads to anxiety.
2025-07-31 | GSE284463 | GEO
Project description: Not available
| S-EPMC12582363 | biostudies-literature
Project description:Global expression profiling of epileptogenesis has been confounded by variability across laboratories, epilepsy models, tissue sampled and experimental platforms, with the result that very few genes demonstrate consistent expression changes. The present study minimizes these confounds by combining Affymetrix microarray datasets from seven laboratories, using three status epilepticus (SE) models of epilepsy in rats (pilocarpine, kainate, self-sustained SE or SSSE) and the rat kindling model. Total RNA was harvested from laser-captured dentate granule cells from 6 rats at three times during the early-to-mid latent phase that precedes epilepsy symptoms in the SE models (1, 3 and 10 days after SE), or 24 hr after the first stage 2, stage 4 and stage 5 seizure in the kindling model. Each epilepsy model was studied in two independent laboratories except SSSE. The initial goals of this study were to a) identify model-independent transcriptional changes in dentate granule cells that could point to novel intervention targets for epileptogenesis, b) characterize the basal transcriptional profile of dentate granule cells, and c) identify genes that have highly variable expression. Each experimental group consists of 6 rats (biological replicates) from one laboratory at a single time point, except for the SSSE group (6 at day 1 after SSSE, 5 controls and at day 3 after SSSE, 4 at day 10). Thus granule cells were harvested from 164 rats.
2013-06-08 | E-GEOD-47752 | biostudies-arrayexpress
Project description:Global expression profiling of epileptogenesis has been confounded by variability across laboratories, epilepsy models, tissue sampled and experimental platforms, with the result that very few genes demonstrate consistent expression changes. The present study minimizes these confounds by combining Affymetrix microarray datasets from seven laboratories, using three status epilepticus (SE) models of epilepsy in rats (pilocarpine, kainate, self-sustained SE or SSSE) and the rat kindling model. Total RNA was harvested from laser-captured dentate granule cells from 6 rats at three times during the early-to-mid latent phase that precedes epilepsy symptoms in the SE models (1, 3 and 10 days after SE), or 24 hr after the first stage 2, stage 4 and stage 5 seizure in the kindling model. Each epilepsy model was studied in two independent laboratories except SSSE. The initial goals of this study were to a) identify model-independent transcriptional changes in dentate granule cells that could point to novel intervention targets for epileptogenesis, b) characterize the basal transcriptional profile of dentate granule cells, and c) identify genes that have highly variable expression.
2013-06-08 | GSE47752 | GEO
Project description:Immature dentate granule cells (DGCs) generated in the hippocampus during adulthood are believed to play a unique role in dentate gyrus function. Although immature DGCs have hyperexcitable membrane properties in vitro, the consequences of this hyperexcitability in vivo remain unclear. In particular, the relationship between experiences that activate the dentate gyrus, such as exploration of a novel environment (NE), and downstream molecular processes that modify dentate gyrus circuitry in response to cellular activation are unknown in this cell population. We first performed quantification of immediate early gene proteins in immature (5-week-old) and mature (13-week-old) DGCs from mice exposed to a NE. Paradoxically, we observed lower immediate early gene protein expression in hyperexcitable immature DGCs. We then isolated nuclei from active and inactive immature DGCs and performed single nuclei RNA-Sequencing. Compared to mature nuclei collected from the same animal, immature DGC nuclei showed less activity-induced transcriptional change, even though they were classified as active based on expression of ARC protein. These results demonstrate that the coupling of spatial exploration, cellular activation, and transcriptional change differs between immature and mature DGCs, with blunted activity-induced changes in immature cells.
2023-02-23 | GSE214309 | GEO
Project description:The risk for psychiatric disorders is strongly affected by environmental stressors. The underlying mechanisms are inevitably multifactorial still not fully understood. Glucocorticoids (GCs), which are prominent stress mediators that affect transcriptional activity and brain morphology, are implicated in the pathophysiology of multiple forms of psychopathology. The challenge is that of establishing the relevance of GC-related transcriptional effects for stress-related psychopathology in humans. We addressed this issue by generating gene expression data from hippocampal dentate gyrus from macaques and rats to identify clusters of co-expressed genes sensitive to GC exposure as the basis for a biologically-informed polygenic risk score (ePRS) to investigate neuropsychiatric outcomes in humans exposed to early life adversity. We used RNA-sequencing data to identify a cluster of GC-responsive genes co-expressed in the posterior dentate gyrus (pDG) of female Cynomologus monkeys and preserved in the rat model with the homologous region (the dorsal DG). In total 11395 SNPs derived from these genes (507 genes) were used to create an ePRS to explore the interaction with early life adversity on psychiatric phenotypes in human cohorts using the UK Biobank Resource and ALSPAC data sets. The biologically-informed ePRS significantly predicted psychotic behavior in adversity-exposed females as well as variation in brain volume. These findings reveal that GC exposure influences a specific group of genes in pDG, largely enriched for transcription processes and pathways related to development activity. Variations in the expression of this gene network can be used in a translational manner to predict risk for neuropsychiatric conditions and brain volume alterations after early stress exposure. These results highlight the importance of hippocampal GC-related transcriptional activity as a mediator for the effects of early life adversity on mental health outcomes.
2020-05-29 | GSE151342 | GEO
Project description:Hippocampal sclerosis (HS) is the most common neuropathological finding of medically intractable cases of mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsy. Within the dentate gyrus, HS may be associated with granule cell dispersion and aberrant mossy fiber sprouting, and these pathological changes are accompanied by a range of molecular changes. In this study, we analyzed the gene expression profiles of dentate granule cells of MTLE patients with and without HS to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations and to shed light on the transcriptional changes associated with HS. 12 samples of dentate granule cells from patients with mesial tempora lobe epilepsy, 5 with hippocampal sclerosis and 7 without hippocampal sclerosis. 10 samples had replicates.
2016-06-29 | E-GEOD-71058 | biostudies-arrayexpress
Project description:Childhood adversity has an impact on multiple sclerosis (MS) onset, clinical severity and progression, but our understanding of potentially related biological pathways is limited. This study evaluated 60 individuals with either pediatric-onset MS (POMS) or adult-onset MS (AOMS) and tested the association between personal history of childhood adversity and clinical MS outcomes, current indicators of allostatic load, and epigenetic signatures. We conceptualized childhood adversity for each participant as a composite of individual, family, and socioeconomic measures captured, respectively, by the Adverse Childhood Experiences questionnaire, level of parental education, and estimated household income during childhood. Our primary goal was to test the association between a history of childhood adversity and MS symptom severity, degree of neurologic impairment, biomarkers of allostatic load, and epigenetic changes. We found that participants with a history of childhood adversity were more likely to have greater MS symptom burden and greater disability but did not differ in allostatic load. Among all patients, epigenetic signatures did not differ by history of childhood adversity. However, when we further analyzed by MS subtype (POMS vs. AOMS), we found that the POMS participants with childhood adversity had epigenetic signatures characterized by increased methylated regions. In contrast, AOMS individuals with childhood adversity showed decreased methylation compared to individuals without childhood adversity. None of the observed clinical and biologic differences were explained by differences in access to or timing of the onset of MS therapy or by the interval between symptom onset and diagnosis . Our findings suggest that individuals with MS who experienced childhood adversity may have an increased MS symptom burden and greater neurologic deficits. A history of childhood adversity was associated with DNA methylation patterns specific to POMS vs. AOMS. These findings suggest that the biologic and clinical consequences of childhood adversity may have varying effects throughout the MS lifespan.
2026-06-16 | GSE306738 | GEO