![]() Astrocytes also make a crucial contribution to communication, operating within glial networks through gap junctions and hemichannels and bidirectionally with neurons and endothelial cells via diffusible and surface molecules. Through an array of transporters, ion channels and released and adhesion molecules, astrocytes play key roles in the regulation of extracellular fluid homeostasis, integrity of the blood–brain barrier and assurance of metabolic demand and antioxidant defense of neurons. Mature astrocytes ensheath synapses and fine blood vessels, within the neuro-glio-vascular units, to shape the functional micro-architecture of the central nervous system (CNS). Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks. These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. 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. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. 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. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. ![]() CAMP signaling produces dramatic changes in astrocyte morphology and physiology. ![]()
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