Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Environmental control of astrocyte pathogenic activities in CNS inflammation

ABSTRACT: Environmental control of astrocyte pathogenic activities in CNS inflammation

PROVIDER: PRJNA503633 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation.

Project description:Genome-wide studies have identified genetic variants linked to neurologic diseases. Environmental factors also play important roles, but no methods are available for their comprehensive investigation. We developed an approach that combines genomic data, screens in a novel zebrafish model, computational modeling, perturbation studies, and multiple sclerosis (MS) patient samples to evaluate the effects of environmental exposure on CNS inflammation. We found that the herbicide linuron amplifies astrocyte pro-inflammatory activities by activating signaling via sigma receptor 1, inositol-requiring enzyme-1α (IRE1α), and X-box binding protein 1 (XBP1). Indeed, astrocyte-specific shRNA- and CRISPR/Cas9-driven gene inactivation combined with RNA-seq, ATAC-seq, ChIP-seq, and study of patient samples suggest that IRE1α-XBP1 signaling promotes CNS inflammation in experimental autoimmune encephalomyelitis (EAE) and, potentially, MS. In summary, these studies define environmental mechanisms that control astrocyte pathogenic activities and establish a multidisciplinary approach for the systematic investigation of the effects of environmental exposure in neurologic disorders.

| S-EPMC6440749 | biostudies-literature

Environmental control of astrocyte pathogenic activities in CNS inflammation

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-01-18 | GSE122119 | GEO

Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities

Project description:Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities

| PRJNA759190 | ENA

Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities [ChIP-seq]

Project description:Atmospheric Particulate Matter (PM) is one of the leading environmental risk factors for the global burden of disease. Increasing epidemiological studies demonstrated that PM plays a significant role in CNS demyelinating disorders; however, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that PM exposure aggravates neuroinflammation, myelin injury, and dysfunction of movement coordination ability via boosting microglial pro-inflammatory activities, in both the pathological demyelination and physiological myelinogenesis animal models. Indeed, pharmacological disturbance combined with RNA-seq and ChIP-seq suggests that TLR-4/NF-κB signaling mediated a core network of genes that control PM-triggered microglia pathogenicity. In summary, our study defines a novel atmospheric environmental mechanism that mediates PM-aggravated microglia pathogenic activities, and establishes a systematic approach for the investigation of the effects of environmental exposure in neurologic disorders.

2022-02-23 | GSE183097 | GEO

Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities [RNA-seq]

2022-02-23 | GSE183098 | GEO

Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [astrocyte]

Project description:Astrocyte activation is associated with progressive inflammatory demyelination in multiple sclerosis (MS). The molecular mechanisms underlying astrocyte activation remain incompletely understood. Recent studies have suggested that classical neurotransmitter receptors are implicated in the modulation of brain innate immunity. We investigated the role of dopamine signaling in the process of astrocyte activation. Here, we show the upregulation of dopamine D2 receptor (DRD2) in reactive astrocytes in MS brain and non-canonical role of astrocytic DRD2 in MS pathogenesis. Mice deficient in astrocytic Drd2 exhibit a remarkable suppression of reactive astrocytes and inflammation which are highly correlated with the amelioration of experimental autoimmune encephalomyelitis (EAE). Mechanistically, DRD2 regulates the expression of 6-pyruvoyl-tetrahydropterin synthase which modulates NF-κB activity through protein kinase C-δ. Pharmacological blockade of astrocytic DRD2 with a DRD2 antagonist dehydrocorybulbine remarkably inhibits the inflammatory response in mice lacking Drd2 in neurons. Together, our findings reveal previously uncharted roles for a DRD2 in astrocyte activation during EAE-associated CNS inflammation. Its therapeutic inhibition may provide a potent lever to alleviate autoimmune diseases.

2022-07-15 | GSE205290 | GEO

Astrocyte-produced HB-EGF limits autoimmune CNS pathology

Project description:Astrocyte-produced HB-EGF limits autoimmune CNS pathology

| PRJNA1028105 | ENA

Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities [ChIP-seq]

Project description:Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities [ChIP-seq]

| PRJNA759196 | ENA

Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities [RNA-seq]

Project description:Atmospheric particulate matter aggravates CNS demyelination via TLR-4/NF-κB-mediated microglia pathogenic activities [RNA-seq]

| PRJNA759197 | ENA

Astrocyte-produced HB-EGF limits autoimmune CNS pathology [WGBS]

Project description:Astrocyte-produced HB-EGF limits autoimmune CNS pathology [WGBS]

| PRJNA1028108 | ENA