title: cAMP response element-binding protein regulates differentiation and survival of newborn neurons in the olfactory bulb.
abstract: The transcription factor cAMP response element-binding protein (CREB) is involved in multiple aspects of neuronal development and plasticity. Here, we demonstrate that CREB regulates specific phases of adult neurogenesis in the subventricular zone/olfactory bulb (SVZ/OB) system. Combining immunohistochemistry with bromodeoxyuridine treatments, cell tracer injections, cell transplants, and quantitative analyses, we show that although CREB is expressed by the SVZ neuroblasts throughout the neurogenic process, its phosphorylation is transient and parallels neuronal differentiation, increasing during the late phase of tangential migration and decreasing after dendrite elongation and spine formation. In vitro, inhibition of CREB function impairs morphological differentiation of SVZ-derived neuroblasts. Transgenic mice lacking CREB, in a null CREM genetic background, show reduced survival of newborn neurons in the OB. This finding is further supported by peripheral afferent denervation experiments resulting in downregulation of CREB phosphorylation in neuroblasts, the survival of which appears heavily impaired. Together, these findings provide evidence that CREB regulates differentiation and survival of newborn neurons in the OB.
authors.affiliation: Department of Animal and Human Biology, University of Turin, 10123 Turin, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Giachino
authors.forename: Silvia
authors.initials: S
authors.lastname: De Marchis
authors.forename: Costanza
authors.initials: C
authors.lastname: Giampietro
authors.forename: Rosanna
authors.initials: R
authors.lastname: Parlato
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perroteau
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
authors.forename: Aldo
authors.initials: A
authors.lastname: Fasolo
authors.forename: Paolo
authors.initials: P
authors.lastname: Peretto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein