title: Post-natal Deletion of Neuronal cAMP Responsive-Element Binding (CREB)-1 Promotes Pro-inflammatory Changes in the Mouse Hippocampus.
abstract: By taking advantage of a "floxed" conditional CREB mutant mouse (CREB1loxP/loxP), in which postnatal deletion of the Creb gene in the forebrain is driven by the calcium/calmodulin-dependent protein kinase II-α gene (Camk2a) promoter (BCKO mice), we here show that selective disruption of CREB function in adult forebrain neurons results, in adult mice, in morphological alterations at the hippocampal level, including hippocampal shrinkage, reduced somal volume of neurons, microgliosis and mild reactive astrocytosis, mainly involving the CA1 subfield. The huge increase of microglial cells showing a mild activated profile, and the higher percentage of double-stained GFAP/S100B astrocytes, together with the increased expression of S100b mRNA at hippocampal level, suggest the establishment of a sub-inflammatory environment in the hippocampus of BCKO mice compared with age-matched controls. Collectively, the present data link neuron-specific, adult deletion of CREB to hippocampal structural alterations and to the early appearance of neuropathological features closely resembling those occurring in the aged brain. This information may be valuable for the understanding of the role of CREB in neuroinflammatory pathways.
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Marchese
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Maria
authors.affiliation: Institute of General Pathology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Samengo
authors.affiliation: Institute of General Pathology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Pani
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy. fabrizio.michetti@unicatt.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Michetti
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy. mariaconcetta.geloso@unicatt.it.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Geloso
mesh_terms: D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency* / Q000235:genetics; D017353:Gene Deletion; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018836:Inflammation Mediators
keywords: Astroglia; Hippocampus; Microglia; Neuroinflammation; S100B; cAMP responsive-element binding (CREB)