Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes.
BACKGROUND
cAMP 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.


RESULTS
Here 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.


CONCLUSIONS
These 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.
Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona, E-08028, Spain.|Present address: Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, E-08950, Spain.
Sonia
S
Paco
Centre for Genomic Regulation, Barcelona, E-08003, Spain.|Present address: Division of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 581, D-69120, Heidelberg, Germany.
Manuela
M
Hummel
Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona, E-08028, Spain.|Institute of Neurosciences, University of Barcelona, Barcelona, E-08035, Spain.
Virginia
V
Plá
Institute for Predictive and Personalized Medicine of Cancer, Badalona, E-08916, Spain.|Germans Trias i Pujol Health Sciences Research Institute, E-08916, Badalona, Spain.
Lauro
L
Sumoy
Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona, E-08028, Spain. faguado@ub.eduAQ2.|Institute of Neurosciences, University of Barcelona, Barcelona, E-08035, Spain. faguado@ub.eduAQ2.
Fernando
F
Aguado
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation
D000975:Antioxidants; D000242:Cyclic AMP
Antioxidant defense; Astrocytes; Brain; Differentiation; NR2C; Reactive glia; Transcriptomic; cAMP