title: ATP and noradrenaline activate CREB in astrocytes via noncanonical Ca(2+)  and cyclic AMP independent pathways.
abstract: In neurons, it is well established that CREB contributes to learning and memory by orchestrating the translation of experience into the activity-dependent (i.e., driven by neurotransmitters) transcription of plasticity-related genes. The activity-dependent CREB-triggered transcription requires the concerted action of cyclic AMP/protein kinase A and Ca(2+) /calcineurin via the CREB-regulated transcription co-activator (CRTC). It is not known, however, whether a comparable molecular sequence occurs in astrocytes, despite the unquestionable contribution of these cells to brain plasticity. Here we sought to determine whether and how ATP and noradrenaline cause CREB-dependent transcription in rat cortical astrocyte cultures. Both transmitters induced CREB phosphorylation (Western Blots), CREB-dependent transcription (CRE-luciferase reporter assays), and the transcription of Bdnf, a canonical regulator of synaptic plasticity (quantitative RT-PCR). We indentified a Ca(2+) and diacylglycerol-independent protein kinase C at the uppermost position of the cascade leading to CREB-dependent transcription. Notably, CREB-dependent transcription was partially dependent on ERK1/2 and CRTC, but independent of cyclic AMP/protein kinase A or Ca(2+) /calcineurin. We conclude that ATP and noradrenaline activate CREB-dependent transcription in cortical astrocytes via an atypical protein kinase C. It is of relevance that the signaling involved be starkly different to the one described in neurons since there is no convergence of Ca(2+) and cyclic AMP-dependent pathways on CRTC, which, moreover, exerts a modulatory rather than a central role. Our data thus point to the existence of an alternative, non-neuronal, glia-based role of CREB in plasticity.
authors.affiliation: Institut de Neurociències, Universitat Autònoma de Barcelona, Spain.
authors.forename: Paulina
authors.initials: P
authors.lastname: Carriba
authors.forename: Luis
authors.initials: L
authors.lastname: Pardo
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Parra-Damas
authors.forename: Mathieu P
authors.initials: MP
authors.lastname: Lichtenstein
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Saura
authors.forename: Aurora
authors.initials: A
authors.lastname: Pujol
authors.forename: Roser
authors.initials: R
authors.lastname: Masgrau
authors.forename: Elena
authors.initials: E
authors.lastname: Galea
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005576:Colforsin; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine