Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytesReport as inadecuate




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BMC Genomics

, 17:304

Human and rodent genomics

Abstract

BackgroundcAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown.

ResultsHere we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo–like transcriptional features to cultured astrocytes.

ConclusionsThese results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.

KeywordsAntioxidant defense Astrocytes cAMP Differentiation Reactive glia Transcriptomic Brain NR2C AbbreviationsFDRfalse discovery rate

GFAPglial fibrillary acidic protein

GSEAgene set enrichment analysis

NESnormalized enrichment score

NR2CNMDA receptor subunit 2C.

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-016-2623-4 contains supplementary material, which is available to authorized users.

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Author: Sonia Paco - Manuela Hummel - Virginia Plá - Lauro Sumoy - Fernando Aguado

Source: https://link.springer.com/







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