title: CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
abstract: The 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.
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas, Sant Joan d'Alacant, Spain.
authors.forename: Jose P
authors.initials: JP
authors.lastname: Lopez-Atalaya
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ciccarelli
authors.forename: Jose
authors.initials: J
authors.lastname: Viosca
authors.forename: Luis M
authors.initials: LM
authors.lastname: Valor
authors.forename: Maria
authors.initials: M
authors.lastname: Jimenez-Minchan
authors.forename: Santiago
authors.initials: S
authors.lastname: Canals
authors.forename: Maurizio
authors.initials: M
authors.lastname: Giustetto
authors.forename: Angel
authors.initials: A
authors.lastname: Barco
mesh_terms: D000107:Acetylation; D000818:Animals; D001522:Behavior, Animal; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D003071:Cognition; D005260:Female; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse