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

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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.

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Acknowledgements

This work was supported by funds from Università Cattolica del S. Cuore to F.M. (Linea D3.2 2013). The Authors wish to thank E. Guadagni and D. Bonvissuto for excellent technical support.

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Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy

    Elisa Marchese, Valentina Di Maria, Fabrizio Michetti & Maria Concetta Geloso

  2. Institute of General Pathology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168, Rome, Italy

    Daniela Samengo & Giovambattista Pani

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  1. Elisa Marchese
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  2. Valentina Di Maria
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  3. Daniela Samengo
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  4. Giovambattista Pani
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  5. Fabrizio Michetti
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  6. Maria Concetta Geloso
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Correspondence to Fabrizio Michetti or Maria Concetta Geloso.

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Prof. Fabrizio Michetti, Dr. Maria Concetta Geloso and Dr. Giovambattista Pani share the senior authorship.

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Marchese, E., Di Maria, V., Samengo, D. et al. Post-natal Deletion of Neuronal cAMP Responsive-Element Binding (CREB)-1 Promotes Pro-inflammatory Changes in the Mouse Hippocampus. Neurochem Res 42, 2230–2245 (2017). https://doi.org/10.1007/s11064-017-2233-9

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