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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience IV

ABSTRACT: Pharmacological inhibition of cGAS with TDI-6570 protected against the synaptic loss and cognitive deficits in P301S tauopathy model, likely via enhancing MEF2C transcriptional network and associated cognitive resilience

ORGANISM(S): Mus musculus

PROVIDER: GSE226383 | GEO | 2023/04/26

REPOSITORIES: GEO

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience II

Project description:Here we report that activation of cyclic GMP-AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of cGAS in tauopathy mice diminished microglial IFN-I response, preserved synapse integrity and plasticity, and protected against cognitive impairment without affecting the pathogenic tau load. cGAS ablation enhanced, while activation of IFN-I downregulated, neuronal MEF2C expression network linked with cognitive resilience in AD.

2023-04-26 | GSE226381 | GEO

Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience I

Project description:Analysis of differentially expressed genes (DEGs) revealed a striking upregulation of interferon genes in P301S, compared to non-transgenic hippocampi, and enrichment of transcription factor motifs of interferon-response factors (IRFs) and interferon-sensitive response elements (ISREs). Cgas deletion reduced the induction of a subset of tau-stimulated inflammatory and cytokine expression including interferon stimulated genes such as Stat1, Ddx60, Isg20, Rnf213, Parp12, Ifi35, and Sp100. Thus, microglial cGAS promotes IFN-I expression in response to tau.

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience

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

2023-04-26 | GSE226385 | GEO

Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience III

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience

Project description:Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience I

Project description:Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience I

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience IV

Project description:Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience IV

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience II

Project description:Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience II

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Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience III

Project description:Cyclic GMP-AMP synthase and interferon activation diminish MEF2C-mediated cognitive resilience III

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RNA-seq and TRAP-seq of astrocytes and brain tissue in mouse models of Alzheimer's pathology

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