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

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

PROVIDER: PRJNA844335 | ENA |

REPOSITORIES: ENA

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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

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

2022-07-15 | GSE205291 | GEO

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

Project description:Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis

| PRJNA844329 | ENA

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

Project description:Inhibition of astrocytic DRD2 suppresses CNS inflammation in an animal model of multiple sclerosis [spinal cord]

| PRJNA844336 | ENA

Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

Project description:Astrocytic morphogenesis and maturation are critical steps in CNS development. The time window of astrocyte morphological development is well defined, but the molecular underpinnings are still unclear. BDNF is a critical growth factor involved in the development of the CNS, including synapse refinement. Here we demonstrate the BDNF receptor at Ntrk2 is enriched in astrocytes relative to all CNS cell populations. RNA sequencing indicates Ntrk2 falls in the top 0.001% of all gene transcripts expressed in juvenile astrocytes, almost exclusively due to truncated TrkB.T1. Astrocyte complexity is increased in the presence of BNDF in vitro, which is dependent upon the presence of TrkB.T1. Furthermore, deletion of TrkB.T1 in vivo revealed astrocytes with significantly reduced volume and branching complexities. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis. Together, these data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphogenesis and indicate this signaling may contribute to astrocyte regulation of neuronal synapse development.

2019-08-26 | GSE122176 | GEO

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

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

2022-07-15 | GSE205292 | GEO

Astrocyte-produced HB-EGF limits autoimmune CNS pathology

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

| PRJNA1028105 | ENA

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch (ChIP-Seq)

Project description:Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression, and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrogenic programs while inhibiting Stat3-mediated astrogliogenesis, and thereby regulate phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision. Examination of Hdac3 and p300 genomewide occupancy in differentiating oligodendrocytes

2016-02-21 | E-GEOD-76411 | biostudies-arrayexpress

Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

Project description:Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

| PRJNA503873 | ENA

Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch (RNA-Seq)

Project description:Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression, and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrogenic programs while inhibiting Stat3-mediated astrogliogenesis, and thereby regulate phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision. Gene expression profiling of optic nerve from P12 control and Hdac3 cKO mice

2016-02-21 | E-GEOD-76410 | biostudies-arrayexpress

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