Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Early-life stress impacts the adult microglia transcriptome under basal and inflammatory conditions

ABSTRACT: Early-life stress (ELS) leads to increased vulnerability to psychiatric illness including cognitive impairment later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but, how ELS impacts microglia, the macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS induced by limited bedding and nesting material during the first week of life (P2 – P9) on the morphology and gene expression of microglia from young (postnatal day (P)9) and adult (P200) mice. ELS led to a change in the proportion of morphological microglia subtypes in adulthood, associated with immune reactivity. At the transcriptional level, whereas at P9 no ELS mediated changes were detected, at P200 ELS induced transcriptional changes in microglia genes involved in the immune response and protein ubiquitination. Additionally, ELS altered microglia gene expression changes during development from P9 to P200 and in response to LPS at P200, in both cases marked by GO-terms associated with the immune response. Concluding, these data show that ELS has persistent effects on the morphology and gene expression program of microglia and results in an altered transcriptional response to a systemic LPS challenge.

ORGANISM(S): Mus musculus

PROVIDER: GSE207067 | GEO | 2022/12/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Early Life Stress Restricts Translational Reactivity in CA3 Neurons Associated with Altered Stress Response in Adulthood

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

RNA-sequencing of orbitofrontal cortex following limited bedding and nesting stress model

Project description:RNA-sequencing of the orbitofrontal cortex was performed in male and female rats following exposure to the limited bedding and nesting model of early life adversity.

2024-06-08 | GSE176488 | GEO

Early life stress leads to gene expression down-regulation in prefrontal cortex [RNA-seq]

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

Early life stress leads to gene expression down-regulation in prefrontal cortex [microarray]

2021-12-31 | GSE153042 | GEO

Genomic changes in response to different doses of early life stress in the developing hippocampus

Project description:Early adversity in the form of neglect, abuse, and unpredictable stress impairs hippocampal development across diverse mammalian species. Individuals exposed to multiple adversities are more impacted compared to those exposed to a single adversity. However, the mechanisms responsible for this dose-dependent effect are unclear and have not been investigated in animal models. Here we assess the effects of a single stressor (i.e. limited bedding/nesting) abbreviated as LB and unpredictable multiple stressors (limited bedding/nesting, unpredictable maternal separation, and nest disruption) abbreviated as UPS on gene expression in the hippocampus of 17-day old pups (P17).

2023-12-07 | GSE142305 | GEO

The influence of early life stress on social behavior and transcriptome in the prefrontal cortex.

Project description:Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the function in developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect the function in behavior and transcriptome in PFC. We found that reductions of social interaction, social preference, and social novelty in ELS mice. Moreover, an increase of anxiety-like behavior was observed in ELS mice, but there were no changes in weight and repetitive behavior. To identify the gene involved in social behavior, we conducted transcriptome analysis and identified 15 differentially expressed genes (DEGs) in the PFC of ELS mice. These genes were involved in transcriptional regulation, stress, and synaptic signaling. We also found that a decreased number of neurons and an increased number of microglia in the PFC of ELS mice. These results suggest that ELS affects PFC cytoarchitecture by stress signal transduction and eventually alters mouse behavior. Our study demonstrates that ELS influences behavior, transcriptome and cytoarchitecture in the brain of adolescent mice.

2021-11-30 | GSE180055 | GEO

Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Project description:Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS)to glycolysis, or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells and little is known about the metabolic reprogramming of human microglia. In this study, we investigated the transcriptomic and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We found that both species displayed a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming was characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides the first direct comparison of energy metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.

2023-09-02 | PXD043836 | Pride

Gene Expression Regulation in Brain Underlying Innate Immune Memory

Project description:As the brain’s resident immune cells, microglia upregulate inflammatory gene expression to promote immune functions. Following the response to early life infection, microglia can remain in a “primed” state in which a subsequent immune trigger produces a hyper-activation. Paradoxically, multiple repeated immune activating events can lead to tolerance, the suppression of immune gene expression and function. Both priming and tolerance represent a form of cellular memory that may be disrupted in neurodevelopmental disorders and is largely unexplored in microglia. We hypothesize that acute versus repeated immune activation engages expression of distinct sets of genes, leading to either microglial priming or tolerance. Using in vivo peripheral injections of low dose liposaccharide (LPS 500ug/kg intraperitoneal) to mimic bacterial infection in mice, we compared animals recievig 1, 2, 3, or 4 daily doses of LPS compared to Vehicle (PBS) controls. We examined tissue from three brain regions, the hippocampus, striatum and frotal cortex by RNAseq.

2024-09-25 | GSE165287 | GEO

In-depth quantitative proteomics of signal pathways in BV2 microglial cell activation

Project description:Microglia become activated by disturbances in the homeostasis of their local microenvironment. While there are varying degrees of microglia activation, a pro-inflammatory reactive state induced by exposure to stimuli like LPS and IFN-γ. In this study, we identified a total of 5497 proteins in whole cell proteome and 4938 proteins for secretome of activated BV-2 mouse microglia cell line with LPS or IFN-γ using improved shotgun proteomic approach. From the differentially expressed proteins in stimulated microglia, we were able to classify pathways related immune-inflammatory response or metabolism. Moreover, we performed longitudinal quantification of secreted proteins during the detrimental activation of microglia which releases neurotoxic molecules mediated neuronal cell loss in the brain region.

2017-08-09 | PXD006558 | Pride

Proteomic analysis of alcohol and LPS-treated primary mouse microglia

Project description:Microglia, the resident immune cells of the brain, can exhibit a broad range of activation phenotypes, many of which have been implicated in several diseases and disorders of the central nervous system including alcohol use disorders and disorders. By utilizing a method optimized for sensitive and rapid quantitative proteomic analysis of microglia involving suspension trapping (S-Trap), we were able to produce efficient and reproducible protein extraction from low cell yielding primary mouse brains. Using a ~2 h gradient on a 75 cm UPLC column with a modified data dependent acquisition method on a hybrid quadrupole-Orbitrap mass spectrometer (QE Plus), 5,062 total proteins were identified where 4,928 of those proteins were quantifiable by label-free quantitation (with 5 biological replicates). This analysis resulted in the most comprehensive proteomic dataset for ethanol- and LPS-treated primary mouse microglia to date and even expanded upon the well-characterized macrophage/microglia response to LPS treatment. This study also highlights the subtle, yet significant changes ethanol exposure can induce when compared to control. Interestingly, these changes are not consistent with the robust classical activation induced by LPS treatment, but instead align with the emerging theory that ethanol-treated microglia yield an alternative activation response. The contrast to LPS-treated microglia leads us to conclude that ethanol does not elicit a strong inflammatory response but rather might have a general inhibitory effect on multiple pathways such as phagocytosis and cell migration.

2020-04-07 | PXD014466 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data