CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement

被引:77
|
作者
Lopez-Atalaya, Jose P. [1 ]
Ciccarelli, Alessandro [1 ,2 ,3 ]
Viosca, Jose [1 ]
Valor, Luis M. [1 ]
Jimenez-Minchan, Maria [1 ]
Canals, Santiago [1 ]
Giustetto, Maurizio [2 ,3 ]
Barco, Angel [1 ]
机构
[1] Univ Miguel Hernandez, CSIC, Inst Neurociencias Alicante, Sant Joan dAlacant 03550, Alicante, Spain
[2] Univ Turin, Turin, Italy
[3] Natl Inst Neurosci Italy, Dip Anat Farmacol & Med Legale, Turin, Italy
来源
EMBO JOURNAL | 2011年 / 30卷 / 20期
关键词
CBP; epigenetics; learning and memory; mental retardation; neurogenesis; RUBINSTEIN-TAYBI-SYNDROME; LONG-TERM-MEMORY; ADULT HIPPOCAMPAL NEUROGENESIS; HISTONE ACETYLTRANSFERASE ACTIVITY; SPATIAL-PATTERN SEPARATION; CREB-BINDING-PROTEIN; KNOCKOUT MICE; STIMULATES NEUROGENESIS; DEACETYLASE INHIBITION; SYNAPTIC PLASTICITY;
D O I
10.1038/emboj.2011.299
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:4287 / 4298
页数:12
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