Genomic changes in response to different doses of early life stress in the developing hippocampus
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE142305 | GEO | 2023/12/07
REPOSITORIES: GEO
Similar Datasets
Project description:Using a protocol of chronic early-life stress (ELS) induced by limited bedding and nesting material followed by acute-swim stress (AS) in adulthood, we show that mice with a history of ELS display a blunted CORT response to AS, altered levels of the repressive histone marker H3K9me3 in several hippocampal regions, and a restricted translational response to stress in CA3 neurons
2019-05-31 | GSE131972 | GEO
Project description:The goal of this project was to assess the effects of two paradigms of early life stress on microglial gene expression in the developing hippocampus of 17-day old mice. Sixty thousands microglia were isolated from the hippocampus of 17-day old mice pups exposed to control (CTL), limited bedding (LB) or unpredictable postnatal stress (UPS) conditions and were processed to assess gene expression using the mouse Glia panel (Nanostring, Cat # XT-Mm Glial profiling CSO).
2022-09-28 | GSE190427 | GEO
Project description:Early life adversity has been linked to altered reproductive development in humans, including changes in the timing of pubertal onset and sexual activity. One common form of early life adversity is having limited access to resources. This form of early life adversity can be modeled in rodents using the limited bedding and nesting model (LBN), in which rat dams and pups are placed in a low resource environment from postnatal day (PND) 2 through 9. Our laboratory has previously shown that male rats raised in LBN conditions have elevated levels of plasma estradiol compared to control males. Female rats, on the other hand, show no effect of LBN on plasma hormone levels, pubertal timing, or estrous cycle duration in adulthood. Here, we find that LBN males also show changes in adult reproductive behaviors. LBN males acquired the suite of reproductive behaviors more quickly than their control counterparts over the course of 3 weeks of testing, showing shorter latencies to mount, intromit, and ejaculate compared to controls prior to the final week of testing. We also characterized LBN-induced gene transcription changes across sex in the medial preoptic area (mPOA) which underlies reproductive behaviors. Interestingly, there was no effect of LBN on puberty onset (as measured by preputial separation) or masculinization of the sexually dimorphic nucleus of the preoptic area (SDN/POA; as measured by calbindin immunoreactivity) in males, suggesting LBN may not exert effects on hormone-dependent measures until after puberty.
2022-02-15 | GSE174753 | GEO
Project description:Mental and cognitive health, as well as vulnerability to neuropsychiatric disorders, involve the interplay of genes with the environment during sensitive developmental periods. Genetic and environmental factors contribute to the development and maturation of neurons, synapses, and the resulting brain circuits. Within the hypothalamus, early-life experiences cause changes in the number of excitatory synapses onto corticotropin-releasing hormone (CRH)-expressing neurons in the paraventricular nucleus (PVN). Further, such synaptic changes suffice to induce enduring epigenomic changes within these cells, influencing programs of gene expression. However, the epigenetic mechanisms by which early-life experiences orchestrate transcriptional programs within individual CRH-expressing neurons, with enduring functional consequences, remain unknown. We utilize animal models of an impoverished environment and unpredictable maternal care (in a limited bedding and nesting [LBN] paradigm), which provokes major alterations in cognitive and emotional outcomes. We are focused on the change in gene expression profiles of stress-sensitive CRH-neurons in the PVN following early-life adversity (ELA). Because of the known heterogeneity of CRH-expressing neuronal populations, we are using single-cell RNA sequencing (RNA-seq) to determine differential gene expression associated with early-life adversity and establish the upstream mechanisms and downstream consequences. We found that CRH-expressing populations of neurons in the PVN can be clustered by both their gene expression profiles as well as by their neurotransmitter phenotype. ELA significantly modified gene expression programs in some neuronal clusters more than others, reducing programs of neuronal development and differentiation and enhancing gene families involved in responses to stress and inflammation. The use of single-cell transcriptomics revealed that ELA impacts gene expression profiles in a cell-type specific manner, with distinctive influence on the different clusters and subpopulations of CRH neurons.
2022-05-06 | GSE174085 | GEO
Project description:In a systemic effort to survive environmental stress, organ systems fluctuate and adapt to overcome external pressures. The evolutionary drive back towards homeostasis, makes it difficult to determine if an organism experienced a toxic exposure to stress, especially in early prenatal and neonatal periods of development. Previous studies indicate that primary human teeth may provide historical records of experiences related to stressors during that early time window. To assess the molecular effects of early life adversity on enamel formation, we used a limited bedding and nesting (LBN) mouse model of early life adversity (ELA), to assess changes in enamel organ gene expression and enamel mineralization. Enamel of postnatal day 12 (P12) weight-matched ELA mice was more mineralized as compared control enamel. RNAseq showed 724 genes significantly upregulated in ELA enamel organs as compared to controls, and 574 significantly downregulated genes (DESeq2 p-value <= 0.05). Transcripts expressing the enamel matrix proteins amelogenin (Amelx) and enamelin (Enam) were among the top 4 most differentially expressed genes. The most significantly enriched GO and Reactome pathway was Extracellular Matrix Organization, while the most significantly enriched KEGG Pathways were Butanoate metabolism and Synthesis and Degradation of Ketone Bodies. qPCR analysis of weight-matched ELA and control enamel organs confirmed that expression of the ameloblast-specific proteins Amelx and Enam were highly upregulated in ELA mice. When evaluating molecular mechanisms for amelogenin upregulation, we found significantly increased expression of Dlx3, while transcripts for clock genes Per1 and Nrd1, which have also positively associated with amelogenin expression, were downregulated. These findings suggest that the developing enamel organs are sensitive to the pressures of early life adversity and produce structural biomarkers in tooth enamel mineral to reflect these changes. Together these results support the possibility that tooth enamel may contain biomarkers of cellular effects associated with systemic early life adversity.
2022-04-05 | GSE199982 | GEO
Project description:Early life stress that is not overwhelming can have an “inoculating” effect that promotes resilience in adulthood. However, the mechanisms underlying stress inoculation are unknown and animal models are lacking. Here we used the limited bedding and nesting (LBN) model of adversity to evaluate stress inoculation of addiction-related phenotypes. In LBN, pups from postnatal day 2–9 and their dams were exposed to a low resource environment. In adulthood, they were tested for addiction-like phenotypes and compared to rats raised in standard housing conditions. High levels of impulsivity are associated with substance abuse, but LBN reduced impulsive choice compared to controls in males. LBN males also self-administered less morphine and had a lower breakpoint on a progressive ratio reinforcement schedule than controls. LBN had no effect on addiction-related behavior in females. The nucleus accumbens (NAc) mediates these behaviors, so we tested whether LBN altered NAc physiology in drug-naïve and morphine-exposed rats. LBN reduced sEPSC frequency in males, but not females. Only in males, LBN prevented a morphine-induced increased in the AMPA/NMDA ratio. RNA sequencing and genome-wide assessments of histone modifications were performed to delineate the molecular signature in the NAc associated with LBN-derived phenotypes. LBN produced sex-specific changes in transcription, including in genes related to glutamate transmission. Remodeling of unique histone marks may have contributed to these distinct transcriptional profiles. Collectively, these studies reveal that LBN causes a male-specific stress inoculation effect against addiction-related phenotypes. Identifying factors that promote resilience to addiction may reveal novel treatment options for patients.
2021-02-04 | GSE160495 | GEO
Project description:Early life stress (ELS) is associated with adverse mental health outcomes including anxiety, depression and addiction-like behaviours. While ELS is known to affect the developing brain by leading to increased stress responsiveness and increased glucocorticoid levels, the molecular mechanisms underlying the detrimental effects of ELS remain incompletely characterised. Rodent models have been instrumental in beginning to uncover the molecular and cellular underpinnings of ELS. Limited nesting (LN), an ELS behavioural paradigm with significant improvements over maternal separation, mimics human maternal neglect. We have previously shown that LN leads to anxiety like-behaviours in rats. Here we assessed gene expression changes induced by ELS in rat prefrontal cortex by RNA-sequencing. We show that LN leads primarily to transcriptional repression and identify a molecular signature of LN in rat PFC that is robust to the behavioural paradigm and replicable across rodent species (mouse and rat).
2021-12-31 | GSE153043 | GEO
Project description:Early life stress (ELS) is associated with adverse mental health outcomes including anxiety, depression and addiction-like behaviours. While ELS is known to affect the developing brain by leading to increased stress responsiveness and increased glucocorticoid levels, the molecular mechanisms underlying the detrimental effects of ELS remain incompletely characterised. Rodent models have been instrumental in beginning to uncover the molecular and cellular underpinnings of ELS. Limited nesting (LN), an ELS behavioural paradigm with significant improvements over maternal separation, mimics human maternal neglect. We have previously shown that LN leads to anxiety like-behaviours in rats. Here we assessed gene expression changes induced by ELS in rat prefrontal cortex by RNA-sequencing. We show that LN leads primarily to transcriptional repression and identify a molecular signature of LN in rat PFC that is robust to the behavioural paradigm and replicable across rodent species (mouse and rat).
2021-12-31 | GSE153042 | GEO
Project description:Enamel organ mRNA expression in the limiited bedding and nesting (LBN) mouse model
| PRJNA822400 | ENA
Project description:Melanoma is the deadliest type of skin cancer, characterized by high cellular heterogeneity which contributes to therapy resistance and unpredictable disease outcome. Recently, by correlating Reflectance-Confocal-Microscopy (RCM) morphology with histopathological type, we identified four distinct melanoma-subtypes: dendritic-cell (DC), round-cell (RC), dermal-nest (DN), and combined-type (CT) melanomas. Our results demontsrate that each melanoma subtypes has a distinct biological and gene expression profile, related to tumor aggressiveness, confirming that RCM can be a dependable tool for in vivo detecting different types of melanoma and for early diagnostic screening
2021-11-26 | GSE174395 | GEO