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

Highlights

  • CAMP signaling produces dramatic changes in astrocyte morphology and physiology

  • Before and after treatment cell cultures were essentially formed by astrocytes (>95 % glial fibrillary acidic protein (GFAP)+ cells)

  • Microarray analysis showed that 6221 of 16,594 annotated genes with assigned gene symbol were differentially expressed by a factor of 1.2 or greater in 8Br-cAMP-treated astrocytes

Read more

Summary

Introduction

CAMP signaling produces dramatic changes in astrocyte morphology and physiology. Astrocytes make a crucial contribution to communication, operating within glial networks through gap junctions and hemichannels and bidirectionally with neurons and endothelial cells via. Little is known about the intracellular signaling of astrocytes, and the pathways controlling their differentiation and activation have not been elucidated. By means of STAT transcription factors, cytokines of the interleukin-6 family are key cues in the specification and differentiation of astroglial cells. Smad transcription factors activated by bone morphogenetic proteins promote astrogliogenesis, through their interaction with STAT3 [5]. Analysis of glial activation in pro-inflammatory cytokineadministered and genetically-modified mice has shown that JAK-STAT3 signaling is a key pathway through which astrocytes become reactive [6].

Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.