Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sequencing to determine the effect of neuronal IL-1 receptor knockout and microglia depletion on stress-induced changes to the neuronal transcriptome

ABSTRACT: Chronic stress is associated with increased anxiety, cognitive deficits, and post-traumatic stress disorder. Repeated social defeat (RSD) in mice causes long-term stress-sensitization associated with increased microglia activation, monocyte accumulation, and enhanced interleukin (IL)-1 signaling in endothelia and neurons. With stress-sensitization, mice have amplified neuronal, immune, and behavioral responses to acute stress 24d later. This is clinically relevant as it shares key aspects with post-traumatic-stress-disorder. The mechanisms underlying stress-sensitization are unclear, but enhanced fear memory may be critical. The purpose of this study was to determine the influence of microglia and IL-1R1 signaling in neurons in the development of sensitization and increased fear memory after RSD. The goal of this study was to sequence nuclei from the hippocampus to determine downstream pathways of neuronal IL-1R1 (nIL-1R1) and microglia reactivity.

ORGANISM(S): Mus musculus

PROVIDER: GSE253687 | GEO | 2024/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Microglial RNA-sequencing after stress-sensitization by repeated social defeat

Project description:Stress is associated with an increased prevalence of anxiety and depression. Repeated social defeat (RSD) stress in mice increases the release of monocytes from the bone marrow that are recruited to the brain by microglia. These monocytes enhance inflammatory signaling and augment anxiety. Moreover, RSD promotes stress sensitization, in which exposure to acute stress 24 days after cessation of RSD causes anxiety recurrence. The purpose of this study was to determine whether microglia were critical to stress sensitization and exhibited altered gene expression 24 days after RSD.

2018-12-21 | GSE124169 | GEO

Sequencing to determine the effect of neuronal IL-1b receptor knockout on the stress effect of paired fighting social defeat in mice

Project description:Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell types. Neuronal IL-1R1 is prominently expressed on the neurons of the dentate gyrus, but its role in mediating behavioral responses to stress is unknown. We hypothesize that IL-1 acts on this subset of hippocampal neurons to influence cognitive and mood alterations with stress. Here, mice subjected to psychosocial stress showed reduced social interaction and impaired working memory, and these deficits were prevented by global IL-1R1 knockout. Selective deletion of IL-1R1 in glutamatergic neurons (nIL-1R1-/-), abundant in the hippocampus wherein the inflammatory-influenced effects were observed, abrogated the stress-induced deficits in social interaction and working memory. RNA-sequencing of microdissected hippocampi revealed that stress increased several canonical pathways (TREM1, NF-κ, complement, IL-6 signaling) and upstream regulators (INFγ, IL-1β, NF-κB, MYD88) associated with inflammation. The inductions of TREM1 signaling, complement, and leukocyte extravasation with stress were reversed by nIL-1R1-/-. Collectively, we show that stress-dependent IL-1R1 signaling in hippocampal neurons represents a novel mechanism by which inflammation is perpetuated and social interactivity and working memory are modulated.

2020-04-24 | GSE149195 | GEO

Single Cell RNAseq of the hippocampus after RSD following microglia depletion

Project description:Chronic stress is associated with anxiety and cognitive impairment. Repeated social defeat (RSD) in mice induces anxiety-like behavior driven by microglia and the recruitment of inflammatory monocytes to the brain. Nonetheless, it is unclear how microglia communicate with other cells to modulate the physiological and behavioral responses to stress. Using single-cell (sc)RNAseq, novel stress-associated microglia were identified in the hippocampus and defined by RNA profiles of cytokine/chemokine signaling, cellular stress, and phagocytosis. Microglia depletion with a CSF1R antagonist (PLX5622) attenuated the stress-associated profile of leukocytes, endothelia, and astrocytes. Furthermore, RSD-induced social withdrawal and cognitive impairment were microglia dependent, but social avoidance was microglia independent. Furthermore, single-nuclei (sn)RNAseq showed robust responses to RSD in hippocampal neurons that were both microglia dependent and independent. Notably, stress-induced CREB, oxytocin, and glutamatergic signaling in neurons were microglia dependent. Collectively, these stress-associated microglia influenced transcriptional profiles in the hippocampus linked to social and cognitive deficits.

2024-10-02 | GSE275205 | GEO

Noncanonical Il-1β maturation in microglia impairs cognition in chronic kidney disease via neuronal IL1R signaling

Project description:While cognitive impairment is common in peripheral diseases such as chronic kidney disease (CKD), mechanistic insights and effective therapies are lacking. Here, we show that microglial potassium (K+) dyshomeostasis induces noncanonical IL-1β maturation and neuronal dysfunction via IL-1R signaling in CKD. Despite inflammasome activation in the brain, microglial caspase-1 deficiency does not improve inflammation and cognition in CKD mice. Noncanonical IL-1β maturation in microglia is mediated by the cathepsin C–caspase-8 pathway. Restoring K+ homeostasis in microglia or genetically inhibiting neuronal IL-1R1 signaling abolishes CKD-induced cognitive impairment. Microglial K+ dyshomeostasis and noncanonical microglial IL-1β maturation may therefore be druggable targets in some forms of cognitive impairment. These insights identify a new intercellular microglia–neuron crosstalk and identify potential therapeutic targets to combat inflammasome-induced neuronal dysfunction.

2022-11-26 | GSE218613 | GEO

Sex-specific fear acquisition following early life stress is linked to amygdala and hippocampal purine and glutamate metabolism

Project description:Early life stress (ELS) can negatively impact health, increasing the risk of stress-related disorders, such as post-traumatic stress disorder (PTSD). Importantly, PTSD disproportionately affects women, emphasizing the critical need to explore how sex differences influence the genetic and metabolic neurobiological pathways underlying trauma-related behaviors. This study uses the limited bedding and nesting (LBN) paradigm to model ELS and investigate its sex-specific effects on fear memory formation. Employing innovative unsupervised behavioral classification, the current study reveals distinct behavioral patterns associated with fear acquisition and retrieval in male and female mice following ELS. Females exposed to LBN display heightened active fear responses, contrasting with males. Furthermore, the study examined the crucial link between behavioral regulation and cellular metabolism in key brain regions involved in fear and stress processing. Sex-specific and stress-dependent alterations were observed in purine, pyrimidine, and glutamate metabolism within the basolateral amygdala, the dorsal hippocampus, and the ventral hippocampus. These findings provide crucial insights into the complex interplay between metabolic pathways, the neurobiological underpinnings of fear memory, and stress responses. Importantly, they emphasize the significance of considering sex-specific metabolic alterations when investigating stress-related disorders, opening potential avenues for the development of targeted interventions.

2024-11-20 | MSV000096480 | MassIVE

H3Africa - Trauma And Neurobiology: Maternal stress and transgenerational impact. Search for Epigenetic Markers

Project description:This project aims to characterize the transgenerational genomic impact of genocide exposure and post-traumatic stress disorder (PTSD) in women survivors of the Rwandan genocide and their offspring.

| EGAS00001006645 | EGA

CPEB3-dowregulated Nr3c1 mRNA translation confers resilience to developing posttraumatic stress disorder-like behavior in fear-conditioned mice

Project description:Susceptibility or resilience to posttraumatic stress disorder (PTSD) depends on one’s ability to appropriately adjust synaptic plasticity for coping with the traumatic experience. Activity-regulated mRNA translation synthesizes plasticity-related proteins to support long-term synaptic changes and memory. Hence, cytoplasmic polyadenylation element-binding protein 3-knockout (CPEB3-KO) mice, showing dysregulated translation-associated synaptic rigidity, may be susceptible to PTSD-like behavior. Here, using a context-dependent auditory fear conditioning and extinction paradigm, we found that CPEB3-KO mice exhibited traumatic intensity-dependent PTSD-like fear memory. A genome-wide screen of CPEB3-bound transcripts revealed that Nr3c1, encoding glucocorticoid receptor (GR), was translationally suppressed by CPEB3. Thus, CPEB3-KO neurons with elevated GR expression exhibited increased corticosterone-induced calcium influx and decreased mRNA and protein levels of brain-derived neurotrophic factor (Bdnf). Moreover, the reduced expression of BDNF was associated with increased GR level during fear extinction in CPEB3-KO hippocampi. Intracerebroventricular delivery of BDNF before extinction training mitigated spontaneous fear intrusion in CPEB3-KO mice during extinction recall. Analysis of two GEO datasets revealed decreased transcriptomic expression of CPEB3 but not NR3C1 in peripheral blood mononuclear cells of humans with PTSD. Collectively, this study reveals that CPEB3, as a potential PTSD-risk gene, downregulates Nr3c1 translation to maintain proper GR-BDNF signaling for fear extinction.

2021-04-26 | GSE159731 | GEO

Anakinra restores cellular proteostasis by coupling mitochondrial redox balance to autophagy

Project description:Autophagy selectively degrades aggregation-prone misfolded proteins caused by defective cellular proteostasis. However, the complexity of autophagy may prevent the full appreciation of how its modulation could be used as a therapeutic strategy in disease management. Here we define a molecular pathway through which recombinant interleukin-1 receptor antagonist (IL-1Ra, anakinra) affects cellular proteostasis independently from the IL-1 receptor (IL-1R1). Anakinra promoted H2O2-driven autophagy through a xenobiotic sensing pathway involving the aryl hydrocarbon receptor that, activated through the indoleamine 2,3-dioxygenase 1-kynurenine pathway, transcriptionally activates NADPH Oxidase 4 independent of the IL-1R1. By coupling the mitochondrial redox balance to autophagy, anakinra improved the dysregulated proteostasis network in murine and human cystic fibrosis. We anticipate that anakinra may represent a therapeutic option in addition to its IL-1R1 dependent anti-inflammatory properties by acting at the intersection of mitochondrial oxidative stress and autophagy with the capacity to restore conditions in which defective proteostasis leads to human disease.

2021-11-27 | GSE188809 | GEO

Gene regulation by IL-1β in IL-1R1-deficient mixed glia

Project description:Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, which has diverse actions in the brain as a regulator of host defence responses and a mediator of inflammation. Two major agonists, IL-1α and IL-1β bind to a single known functional (type-1) IL-1 receptor (IL-1RI), which associates with an accessory protein (IL-1RAcP) leading to signal transduction. However, recent evidence suggests that some actions of IL-1 in the brain may be independent of IL-1R1 and its classical signalling pathways, pointing to an as yet unidentified functional receptor for IL-1 expressed in the CNS. In this study, cDNA array based gene expression profiling was used to identify possible genes induced by IL-1β independently of IL-1R1. The results show that IL-1β may indeed regulate some genes independently of IL-1R1, suggesting the presence of additional functional IL-1 receptors in the mouse brain. Keywords: experimental treatment (IL-1β), gene ablation (IL-1R1), glia

2006-03-25 | GSE4507 | GEO

Interleukin-1 contributes to clonal expansion and progression of bone marrow fibrosis in JAK2V617F-induced myeloproliferative neoplasm

Project description:The somatic JAK2V617F mutation is found in a majority of patients with myeloproliferative neoplasms (MPN). Chronic inflammation is often associated with MPN, but the role of inflammation in the pathogenesis of MPN remains elusive. Expression of interleukin-1 (IL-1), a key regulator of inflammation, is found elevated in MPN. Here, we show that increased IL-1β enhances myeloid cell expansion and promotes the development of bone marrow (BM) fibrosis in heterozygous Jak2V617F mouse model of MPN. Genetic deletion of IL-1 receptor 1 (IL-1R1) preferentially inhibited the expansion of Jak2 mutant hematopoietic stem/progenitor cells. Furthermore, IL-1R1 deletion or blockade with anti-IL-1R1 antibody significantly reduced leukocytosis and splenomegaly, and markedly inhibited BM fibrosis in homozygous Jak2V617F mutant mice. Collectively, our results suggest that IL-1 signaling plays an important role in progression to BM fibrosis in MPN, and targeting of IL-1R1 could be a useful strategy for the treatment of myelofibrosis.

2022-08-05 | GSE180339 | GEO

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