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CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
EMBO J., 2011. Aug 16. [Epub ahead of print].

Lopez-Atalaya JP, Ciccarelli A, Viosca J, Valor LM, Jimenez-Minchan M, Canals S, Giustteto M and Barco A.

INA researchers have demonstrated that the gene CBP, which encodes a histone acetyltransferase involved in regulation of gene expression and whose mutations cause a mental retardation disorder, is required for the cognitive enhancement and increased neurogenesis associated to environmental enrichment. This finding has been presented in The EMBO Journal.
The study examines the role of CBP in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Behavioral analyses demonstrated that EE ameliorates some cognitive deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in experience-induced neurogenesis and impaired EE-enhanced spatial navigation and pattern separation ability. These defects correlated with an attenuation of the transcriptional program 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.

 

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