Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1121631 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29356900_1.fastq.gz | Fastqsanger.gz | |||
| SRR29356900_2.fastq.gz | Fastqsanger.gz | |||
| SRR29356901_1.fastq.gz | Fastqsanger.gz | |||
| SRR29356901_2.fastq.gz | Fastqsanger.gz | |||
| SRR29356902_1.fastq.gz | Fastqsanger.gz |
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Project description:Maternal immune activation (MIA)puts offspring at greater risk for neurodevelopmental disorders associated with impaired social behavior. While it is known that immune signaling through the maternal, placental, and fetal compartments contribute to these phenotypical changes, it is unknown to what extent the stress response to illness is involved and how it can be harnessed for potential interventions. To this end, pregnant rat dams were treated with the clinically available 11β-hydroxylase inhibitor metyrapone, alongside administration of the bacterial mimetic lipopolysaccharide (LPS), on gestational day 15. Maternal, placental, and fetal CNS levels of corticosterone and placental 11ßHSD enzymes type 1 and 2 were measured 3-hrs post treatment. Subsequently, offspring social behaviors were measured across critical phases of development. MIA was associated with increased maternal, placental, and fetal CNS corticosterone concentrations that were diminished with metyrapone exposure. Metyrapone protected against reductions in placental 11ßHSD2 in males only, suggesting that less corticosterone was inactivated in female placentas. Behaviorally, metyrapone-exposure protected against MIA-induced social disruptions in juvenile, adolescent, and adult males, while females were unaffected or performed worse. Transcriptomic analyses revealed that metyrapone-exposure triggered opposing effects on gene expression to combat MIA-exposure in males, but not among females. Taken together, these findings illustrate that MIA-induced HPA responses act alongside the immune system to produce behavioral deficits. As a clinical drug already provided to pregnant people and neonates for the treatment of hypercortisolism, the sex-specific benefits and constraints of metyrapone should be investigated further as a potential means of reducing neurodevelopmental risks due to gestational MIA.
2023-08-15 | GSE240604 | GEO
Project description:Maternal immune activation is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment with sub-sequence effects of CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on embryonic day 15. LPS significantly elevated pro-inflammatory cytokines in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-dams exhibited reduced social and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate possible molecular mechanisms by which MIA effects the fetal brain. We observed dysregulation of 3,285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons. 19 Fetal Rat Brain Samples: 10 (-) LPS, 9 (+) LPS.
2012-07-25 | E-GEOD-34058 | biostudies-arrayexpress
Project description:Stress is a major influence on mental health status; the ways that individuals respond to or copes with stressors determine whether they are negatively affected in the future. Stress responses are established by an interplay between genetics, environment, and life experiences. Psychosocial stress is particularly impactful during adolescence, a critical period for the development of mood disorders. In this study we compared two established, selectively-bred Sprague Dawley rat lines, the “internalizing” bred Low Responder (bLR) line versus the “externalizing” bred High Responder (bHR) line, to investigate how genetic temperament and adolescent environment impact future responses to social interactions and psychosocial stress, and how these determinants of stress response interact. Animals were exposed to social and environmental enrichment in adolescence prior to experiencing social defeat and were then assessed for social interaction and anxiety-like behavior. Adolescent enrichment caused bLR rats to display less social avoidance, more social interaction, less submission during defeat, and resilience to the prolonged effects of social stress on corticosterone, while enrichment caused bHR animals to show greater aggression during defeat and during a neutral social encounter, and decreased anxiety-like behavior. To gain insight into the development of social resilience in the anxious phenotype bLRs, RNA-seq was conducted on the hippocampus and nucleus accumbens, two brain regions that mediate stress regulation and social behavior. Gene sets previously associated with stress, social behavior, aggression and exploratory activity were enriched with differential expression in both regions, with a particularly large effect on gene sets that regulate social behaviors. These findings provide further evidence that adolescent enrichment can serve as an inoculating experience against future stressors. The ability to induce social resilience in a usually anxious line of animals by manipulating their environment has translational implications, as it underscores the feasibility of intervention strategies targeted at genetically vulnerable adolescent populations.
2024-05-01 | GSE237890 | GEO
Project description:Human colon organoids were maintained in culture medium alone or exposed to lipopolysaccharide with a combination of three pro-inflammatory cytokines (tumor necrosis factor-a, interleukin-1b and interferon-g [LPS-cytokines]) to mimic the environment in the inflamed colon. Untreated organoids and those exposed to LPS-cytokines were concomitantly treated with a multi-mineral product that has previously been shown to improve barrier structure/function. The organoids were subjected to proteomic analysis to obtain a broad view of the protein changes induced by these interventions. In parallel, confocal fluorescence microscopy and trans-epithelial electrical resistance measurements were used to assess barrier structure/function. The LPS-cytokines altered expression of multiple proteins that influence innate immunity and promote inflammation. Most of these were unaffected by the multi-mineral intervention, though a subset of inflammation-related proteins including fibrinogen-b and -g chains, phospholipase A2 and SPARC was down-regulated in the presence of the multi-mineral intervention; another subset of proteins with anti-inflammatory, antioxidant or anti-microbial activity was up-regulated by multi-mineral treatment. When used alone, the multi-mineral intervention strongly up-regulated proteins that contribute to barrier formation and tissue strength. Concomitant treatment with LPS-cytokines did not inhibit barrier formation in response to the multi-mineral intervention.
2023-06-30 | PXD038941 | Pride
Project description:The gut-brain axis allows gut microbes to influence host social behavior, yet the specific role of microbial genetic variation in this process and its potential transgenerational effects remains poorly understood. Using C. elegans as a model, we identified 77 E. coli strains among 3,983 mutants that markedly enhanced C. elegans aggregation behavior. Our findings reveal that mutant bacteria modulate C. elegans social behavior through distinct neurobehavioral pathways, demonstrating a synergistic regulatory mechanism between microbial genetics and host heredity. Mechanistically, ycgJ mutant bacteria were found to impact C. elegans social behavior via the mitochondrial pathway. Additionally, even F2 offspring of parent C. elegans exposed to these mutant bacteria exhibited enhanced social behavior within their populations. These insights underscore the significance of investigating microbial genetic variation in relation to host behavior, particularly for the development of genetically engineered probiotics, aimed at promoting well-being across generations.
2025-01-27 | GSE283454 | GEO
Project description:Maternal immune activation is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment with sub-sequence effects of CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on embryonic day 15. LPS significantly elevated pro-inflammatory cytokines in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-dams exhibited reduced social and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate possible molecular mechanisms by which MIA effects the fetal brain. We observed dysregulation of 3,285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons.
2012-07-26 | GSE34058 | GEO
Project description:We identify and characterize subgroups of isogenic mouse offspring exposed to identical maternal immune activation induced by gestational administration of the viral mimetic, poly(I:C). We demonstrate that offspring with manifest impairments in social behavior, sensorimotor gating and working memory (“susceptible” offspring) differ from asymptomatic (“resilient” offspring) in terms of their transcriptional profiles in cortical and subcortical brain regions, while displaying only subtle differences in brain morphometry
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Project description:Maternal exposure to social stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. How the effects of maternal social stress are transmitted to the developing foetus is unclear. Using a rat model of maternal social stress during pregnancy, we explored the mechanisms by which maternal stress is conveyed to the foetus and the potential for targeted treatment to prevent disease in the offspring. Maternal stress induced oxidative stress in the placenta, but not in the foetal brain, which was prevented by a single administration of nanoparticle-bound antioxidant prior to the stress exposure. Moreover, this antioxidant treatment prevented prenatal stress-induced anxiety-like behaviour in juvenile male offspring, along with neurological and gene expression changes in the offspring brain. In vitro, placental conditioned medium or foetal plasma from stressed pregnancies caused changes to cultured cortical neurons, similar to those observed in the brains of juvenile offspring exposed to prenatal stress, and were found to contain altered levels of extracellular microRNAs but not corticosterone. The present study highlights the crucial role of the placenta, and molecules secreted from the placenta, in foetal brain development and provides evidence of the potential for treatment that can prevent maternal stress-induced foetal programming of neurological disease.
2024-04-22 | GSE131040 | GEO
Project description:Background Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution of egocentric network sizes (characterized by number of different partners encountered per day). We then used RNA-seq to perform an unbiased assessment of neural differences in gene expression in the prefrontal cortex, the hippocampus and the hypothalamus between these mice with naturally occurring extreme differences in social network size. Results We found that the neurogenomic pathways associated with having extreme social network sizes differed between the sexes. In females, hundreds of genes were differentially expressed between animals with small and large social network sizes, whereas in males very few were. In males, X-chromosome inactivation pathways in the prefrontal cortex were the ones that better differentiated animals with small from those with large social network sizes animals. In females, animals with small network size showed up-regulation of dopaminergic production and transport pathways in the hypothalamus. Additionally, in females, extracellular matrix deposition on hippocampal neurons was higher in individuals with small relative to large social network size. Conclusions Studying neural substrates of natural variation in social behavior in traditional model organisms in their habitat can open new targets of research for understanding variation in social behavior in other taxa.
2020-07-06 | GSE148075 | GEO
Project description:Maternal exposure to stress during pregnancy is associated with an increased risk of psychiatric disorders in the offspring in later life. The mechanisms through which the effects of maternal stress are transmitted to the fetus are unclear, however the placenta, as the interface between mother and fetus, is likely to play a key role. Using a rat model, we investigated a role for placental oxidative stress in conveying the effects of maternal social stress to the fetus and the potential for treatment using a nanoparticle-bound antioxidant to prevent adverse outcomes in the offspring. Maternal psychosocial stress increased circulating corticosterone in the mother, but not in the fetuses. Maternal stress also induced oxidative stress in the placenta, but not in the fetal brain. Blocking oxidative stress using an antioxidant prevented the prenatal stress-induced anxiety phenotype in the male offspring, and prevented sex-specific neurobiological changes, specifically a reduction in dendrite lengths in the hippocampus, as well as reductions in the number of parvalbumin-positive neurons and GABA receptor subunits in the hippocampus and basolateral amygdala of the male offspring. Importantly, many of these effects were mimicked in neuronal cultures by application of placental-conditioned medium or fetal plasma from stressed pregnancies, indicating molecules released from the placenta may mediate the effects of prenatal stress on the fetal brain. Indeed, both placenta-conditioned medium and fetal plasma contained differentially abundant microRNAs following maternal stress, and their predicted targets were enriched for genes relevant to nervous system development and psychiatric disorders. The results highlight placental oxidative stress as a key mediator in transmitting the maternal social stress effects on the offspring's brain and behaviour, and offer a potential intervention to prevent stress-induced fetal programming of affective disorders.
2020-12-01 | GSE130573 | GEO