Maternal antioxidant treatment prevents behavioural and neurological changes in offspring exposed to prenatal social stress
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA540661 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:This SuperSeries is composed of the SubSeries listed below.
2020-12-01 | GSE130574 | 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
Project description:Purpose: Gestational exposure to environmental toxins and socioeconomic stressors are epidemiologically linked to neurodevelopmental disorders with strong male-bias, such as autism. We modeled these prenatal risk factors in mice, by co-exposing pregnant dams to an environmental pollutant and limited-resource stress, which robustly activated the maternal immune system. Only male offspring displayed long-lasting behavioral abnormalities and alterations in the activity of brain networks encoding social interactions. Cellularly, prenatal stressors diminished microglial function within the anterior cingulate cortex, a central node of the social coding network, in males during early postnatal development. Genetic ablation of microglia during the same critical period mimicked the impact of prenatal stressors on a male-specific behavior, indicating that environmental stressors alter neural circuit formation in males via impairing microglia function during development.
2020-10-29 | GSE160344 | GEO
Project description:Prenatal stress (PS) could cause depression of offprsing. Here, relative quantitative phosphoproteomics of hippocampus of PS-S and CON offspring rats were performed using LC-MS/MS to confirm known pathways and identify new areas of depression. A total of 6,790 phosphopeptides, 9,817 phosphorylation sites and 2978 phosphoproteins were detected. Among the 2978 phosphoproteins, 1760 (59.09%) with more than two phosphorylated sites, ENSRNOP00000023460 protein has more than 117 phosphorylated sites, and the average distribution of modification sites per 100 amino acids was 2.97. There were 197 different phophpeptides, including 140 increased phosphopeptides and 57 decreased phosphopeptides in PS-S offspring rats when compared to the CON offspring rats. These differential phosphopeptides corresponded to 100 upregulated and 44 downregulated phosphoproteins respectively. GO enrichment analysis these different phosphoproteins in the first five enrichments of CC category, MF category and BP category were involved in a total of 35 different phosphoproteins and these phosphoproteins were mainly related to myelin, microtubule and synapse associated proteins. The first five enrichment of KEGG pathways were found to be involved in many essential biological pathways, and the first five pathways included amphetamine addiction, insulin secretion, cushing syndrome and circadian entrainment signaling pathway. And these first five pathways were related to nine proteins including Adcy9, Apc, Cacna1c, Camk2a, Camk2b, Camk2g, Ctnnd2, Grin2a, Stx1a. Further research is needed to understand the precise role of these pathways in the depressive-like behavior of offspring rats caused by PS.
2021-12-30 | PXD019117 | Pride
Project description:Following a prenatal stress model, we collected RNA from ileum of offspring at 2 weeks of age. We sequenced the RNA to identify genes that are differentially expressed compared to offspring from unstressed controls. We identified DEGs and a number of biological and signaling pathways in the offsping in response to gesstational stress. We discuss the implications of these stress-induced genes on the development of inflammatory diseases in the gut of the offsping.
2020-06-08 | GSE151966 | GEO
Project description:To investigate whether paternal tobacco smoke (PTS) was associated with prenatal epigenetic programming of CG site methylation, 20 cord blood DNA samples from newborns with and without PTS were subjected to microarray assay of 1,505 CG loci in 807 genes by Illumina GoldenGate® technology bead system to obtain high-throughput DNA Methylation profiles. Samples included 14 newborns without PTS exposure, and 6 newborns with PTS exposure.
2019-04-13 | GSE129751 | GEO
Project description:Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.
2023-11-04 | GSE246534 | GEO
Project description:In this study, we investigated the effects of prenatal bisphenol-A (BPA) exposure on transcriptome profiles in the frontal cortex of the rat offspring. Transcriptome profiling by RNA-seq analysis of frontal cortex tissues isolated from neonatal pups prenatally exposed to BPA revealed that a list of differentially expressed genes (DEGs) associated with autism spectrum disorder (ASD), including Ntng1, Auts2, and Ankrd11 was dysregulated in a sex-specific pattern. The gene ontology analysis revealed that the BPA-responsive genes in the offspring’s frontal cortex were significantly associated with ASD-related neurological functions. These results indicated that prenatal BPA exposure may increase the risk of ASD by impacting ASD-related genes in the offspring’s frontal cortex. We conducted experiments using the frontal cortex from neonatal pups prenatally exposed to BPA or vehicle control (BPA treament; pooled 3 pups frontal cortex, vehicle control; pooled 3 pups frontal cortex). 10-week-old female rats were daily treated with BPA at the concentration of 5,000 microgram/kilogram of maternal body weight or vehicle control from gestation day 1 (GD1) until parturition. Total RNAs were isolated and cDNAs were synthesized. The transcriptome profiles were performed using a high-throughtput RNA-seq.
2023-04-06 | GSE229073 | GEO
Project description:prenatal stress response, genetic modification Background: Prenatal stress (PS) exposure has been shown to increase the risk for emotional disorders in later life. Furthermore, the serotonin transporter (5-HTT) genotype is suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we use a 5-HTT x PS paradigm to investigate whether the effects of PS are dependent upon the 5-HTT genotype. Methods: The effects of PS on cognition, anxiety- and depression-related behaviour were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous (+/-) 5-HTT knockout mice. Additionally, in the female offspring, a genome-wide hippocampal gene expression screening was performed. Results: 5-HTT +/- offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. Conversely, exposure of 5-HTT +/- mice to PS was associated with altered stress-responsivity and increased depressive-like behaviour, particularly in female offspring. Further, 5-HTT genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signalling were regulated by both the 5-HTT +/- genotype and PS exposure, whereas cytokine and Wnt signalling were affected in a 5-HTT genotype x PS manner, indicating a gene x environment interaction at the molecular level. Conclusions: The long-term behavioural effects of PS in C57BL6 mice are partly dependent on the 5-HTT genotype. Further, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioural effects of the 5-HTT genotype, PS exposure, and their interaction. total samples analysed are 12
2011-12-12 | E-GEOD-26025 | biostudies-arrayexpress