title: Nuclear Ca2+ and the cAMP response element-binding protein family mediate a late phase of activity-dependent neuroprotection.
abstract: The mechanism by which physiological synaptic NMDA receptor activity promotes neuronal survival is not well understood. Here, we show that that an episode of synaptic activity can promote neuroprotection for a long time after that activity has ceased. This long-lasting or "late phase" of neuroprotection is dependent on nuclear calcium signaling and cAMP response element (CRE)-mediated gene expression. In contrast, neuroprotection evoked acutely by ongoing synaptic activity relies solely on the activation of the phosphatidylinositol 3-kinase/Akt pathway. This "acute phase" does not require nuclear calcium signaling and is independent of activation of the CRE-binding protein (CREB) family of transcription factors. Thus, activity-dependent neuroprotection comprises two mechanistically distinct phases that differ in their spatial requirements for calcium and in their reliance on the CREB family.
authors.affiliation: Centre for Neuroscience Research, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom.
authors.forename: Sofia
authors.initials: S
authors.lastname: Papadia
authors.forename: Patrick
authors.initials: P
authors.lastname: Stevenson
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hardingham
authors.forename: Hilmar
authors.initials: H
authors.lastname: Bading
authors.forename: Giles E
authors.initials: GE
authors.lastname: Hardingham
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002518:Ceramides / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus; D066298:In Vitro Techniques; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D002518:Ceramides; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018756:GABA Antagonists; D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D049452:Green Fluorescent Proteins; D009118:Muscimol; D013779:Tetrodotoxin; D014212:Tretinoin; D016291:Dizocilpine Maleate; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D002118:Calcium; D001640:Bicuculline