Post-natal Deletion of Neuronal cAMP Responsive-Element Binding (CREB)-1 Promotes Pro-inflammatory Changes in the Mouse Hippocampus

• Published in: Neurochemical research Vol. 42; no. 8; pp. 2230 - 2245
• Main Authors: Marchese, Elisa, Di Maria, Valentina, Samengo, Daniela, Pani, Giovambattista, Michetti, Fabrizio, Geloso, Maria Concetta
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2017; Springer Nature B.V
• Subjects: Age Factors; Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Atrophy - genetics; Atrophy - metabolism; Atrophy - pathology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain; Ca2+/calmodulin-dependent protein kinase II; Calcium; Calcium-binding protein; Calmodulin; Cell Biology; Clonal deletion; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - deficiency; Cyclic AMP Response Element-Binding Protein - genetics; Forebrain; Gene Deletion; Gene expression; Glial fibrillary acidic protein; Gliosis; Hippocampus; Hippocampus - metabolism; Hippocampus - pathology; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - metabolism; Kinases; Male; Mice; Mice, Knockout; Mice, Transgenic; Microglia - metabolism; Microglia - pathology; Microglial cells; mRNA; Neurochemistry; Neurology; Neurons; Neurons - metabolism; Neurons - pathology; Neurosciences; Original Paper; Regulatory sequences; Rodents; S100b protein; Shrinkage; Neuroinflammation; Astroglia; S100B; cAMP responsive-element binding (CREB); Hippocampus; Microglia
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-017-2233-9

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.