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dc.contributor.authorLópez-Atalaya, José P.-
dc.contributor.authorCiccarelli, Alessandro-
dc.contributor.authorViosca, José-
dc.contributor.authorValor, Luis Miguel-
dc.contributor.authorJiménez-Minchan, María-
dc.contributor.authorCanals Gamoneda, Santiago-
dc.contributor.authorGiustetto, Maurizio-
dc.contributor.authorBarco, Ángel-
dc.identifierdoi: 10.1038/emboj.2011.299-
dc.identifierissn: 0261-4189-
dc.identifiere-issn: 1460-2075-
dc.identifier.citationEMBO Journal 30(20): 4287-4298 (2011)-
dc.description.abstractThe epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CREB-binding protein (CBP), a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioural adaptations to environmental enrichment (EE). Morphological and behavioural analyses demonstrated that EE ameliorates deficits associated to CBP deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-mediated enhancement of spatial navigation and pattern separation ability. These defects correlated with an attenuation of the transcriptional programme induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics. © 2011 European Molecular Biology Organization | All Rights Reserved.-
dc.description.sponsorshipResearch at Barco’s laboratory is supported by the grants from the Spanish Ministry of Science and Innovation BFU2008-00611, CSD2007-00023 and SAF2008-03194-E (part of the coordinated ERA-Net NEURON project Epitherapy), and grants from Fundación Ramón Areces and Fundació La Marató de TV3 (063510). SC is supported by grants from the Spanish Ministry of Science and Innovation BFU2009-09938 and CSD2007-00023, and the Fundación Mutua Madrileña (3140/2008). MG is supported by Telethon-Italy (Grant no. GGP09196). JLA has a Juan de la Cierva contract and LMV has a Ramón y Cajal contract both given by the Spanish Ministry of Science and Innovation.-
dc.publisherNature Publishing Group-
dc.titleCBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement-
dc.description.versionPeer Reviewed-
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