Similar Datasets
Project description:We report differentially regulated transcriptome of CD4+ T cells in MIA offspring
2022-01-19 | GSE165693 | GEO
Project description:Open chromatin analysis of CD4+ Tcells from maternal immune activation (MIA) exposed offspring
| PRJNA695468 | ENA
Project description:Transcriptomic analysis of CD4+ Tcells from maternal immune activation (MIA) exposed offspring
| PRJNA695470 | ENA
Project description:To investigate the the underlying molecular mechanisms on how MIA may cause increased anxiety in the female offspring, we carried out RNA-seq on the whole brain of female offspring mice at different developmental stages: just before pregnancy (Preg0), 19 days after pregnancy (Preg19), 2 days after delivery (AD2) and 21 days after delivery (AD21). We then performed gene expression profiling analysis using data obtained from RNA-seq at four time points.
2024-05-25 | GSE233424 | GEO
Project description:Maternal infection and inflammation during pregnancy is associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. We leveraged single-cell RNA sequencing to profile transcriptional changes in the rodent fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis, and stress signaling. We found that MIA specifically activated the integrated stress response (ISR) in male, but not female, MIA offspring, thereby reducing global mRNA translation and altering nascent proteome synthesis. Moreover, genetic blockade of ISR activation rescued the social behavior phenotype in MIA male offspring. Our data suggest that therapeutic targeting of the ISR may be beneficial in reducing maternal inflammation-associated neurodevelopmental disorders.
2020-11-09 | GSE148237 | GEO
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:To determine the transcriptomic changes underlying the MIA microglia phenotype and their reversal by PLX, we performed RNA-sequencing of magnetic CD11B beads-isolated microglia from the whole brain in Saline and MIA male and female offspring at E17, P7, P20, and P60, as well as from MG-REP male and female offspring at P60. Microglial transcriptome reveals novel MIA and repopulation modules and overlap of MIA microglial genes with ASD gene network. 14,225 microglial genes from RNA-seq data revealed distinct transcriptional signatures of immature microglia (IM module, 4681 transcripts, enriched in E17 and P7 Saline), MIA immature microglia (MIA-IM module, 2816 transcripts, enriched in E17 and P7 MIA), Juvenile microglia (JM module, 2318 transcripts, enriched in P20 Saline and MIA), Adult microglia (AM module, 3276 transcripts, enriched in P60 Saline + CTRL, P60 MIA + CTRL and P60 MIA + MG-REP), and repopulated adult microglia (REP-AM module, 1,134 transcripts, enriched in P60 Saline + MG-REP)
2020-03-06 | GSE146526 | GEO
Project description:Background: Environmental insults that activate the maternal immune system are potent primers of developmental neuropathology and maternal immune activation (MIA) has emerged as a risk factor for neurodevelopmental and psychiatric disorders. Animal models of MIA provide an opportunity to identify molecular pathways that initiate disease processes and lead to neuropathology and behavioral deficits in offspring. MIA-induced behaviors are accompanied by anatomical and neurochemical alterations in adult offspring that parallel those seen in affected human populations. Methods: We performed transcriptional profiling and neuroanatomical characterization in a time course across mouse embryonic cortical development, following MIA via single injection of the viral mimic polyinosinic:polycytidylic acid (polyI:C) at E12.5. Transcriptional changes identified in the cortex of MIA offspring at E17.5 were validated and mapped to cortical neuroanatomy and cell types via protein analysis and immunohistochemistry. Results: MIA induced strong transcriptomic signatures, including induction of genes associated with hypoxia, immune signaling, and angiogenesis. The acute response identified 6h after the MIA insult was followed by changes in proliferation, neuronal and glial differentiation, and cortical lamination that emerged at E14.5 and peaked at E17.5. Decreased numbers of proliferative cell types in germinal zones and alterations in neuronal and glial cell types across cortical lamina were identified in the MIA-exposed cortex. Conclusions: MIA-induced transcriptomic signatures in fetal offspring overlap significantly with perturbations identified in neurodevelopmental disorders (NDDs), and provide novel insights into alterations in molecular and developmental timing processes linking MIA and neuropathology, potentially revealing new targets for development of novel approaches for earlier diagnosis and treatment of these disorders.
2021-02-09 | GSE166376 | GEO
Project description:Pregnant dams at embryonic day 11.5 and 12.5 were injected i.p. with saline or polyI:C to induce activation of the maternal immune response. Placentas from each embryo were harvested at several time points relative to the E12.5 injection over the course of gestation to evaluate the placental transcriptome after MIA.
2021-11-30 | GSE149352 | GEO
Project description:A mouse model of maternal immune activation (MIA) is commonly used to study neurodevelopmental disorders. Gene expression analysis has suggested that fetal brain macrophages may be activated by MIA, but it is unclear whether these transcriptional changes connect to behavioral phenotypes in offspring. Here, we have shown that the induction of autism spectrum disorder (ASD)-like behavioral phenotypes by MIA in male offspring is dependent upon fetal activation of the toll-like receptor 3 (TLR3) signaling molecule TRIF. Using single-cell RNA sequencing, we identified a cluster of border-associated macrophages (BAMs) that was significantly enriched in wild-type fetal brains following TLR3-MIA but not diminished in Trif -/- fetal brains. Moreover, after TLR3-MIA, the number of fetal BAMs in the choroid plexus, but not in the meninges, was increased, and these cells were characterized by increased S100a8/9 expression. Finally, we proposed that activation of fetal TLR3-TRIF signaling was induced by transplacental viral infection. Overall, our data suggest that fetal TLR3 signaling contributes to MIA-induced ASD-like behavioral phenotypes in mice.
2022-02-08 | GSE196151 | GEO