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HDAC2 negatively regulates memory formation and synaptic plasticity | |
2009 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
卷号 | 459期号:7243页码:55-U58 |
发表状态 | 已发表 |
DOI | 10.1038/nature07925 |
摘要 | Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment. |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Science & Technology - Other Topics |
WOS类目 | Multidisciplinary Sciences |
WOS记录号 | WOS:000265801300027 |
WOS关键词 | HISTONE DEACETYLASE INHIBITORS ; GENE-EXPRESSION ; MOUSE MODEL ; HUNTINGTONS-DISEASE ; CHROMATIN ; ACETYLATION ; MICE ; MODULATION ; RECEPTORS ; MECHANISM |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120333 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Tsai, Li-Huei |
作者单位 | 1.MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA 2.MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA 3.Harvard Univ, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA 4.MIT, Cambridge, MA 02142 USA 5.Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02142 USA 6.Whitehead Inst Biomed Res, Cambridge, MA 02142 USA 7.MIT, Dept Biol, Cambridge, MA 02139 USA 8.Harvard Univ, Sch Med, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA 9.Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA 10.Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA 11.Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA |
推荐引用方式 GB/T 7714 | Guan, Ji-Song,Haggarty, Stephen J.,Giacometti, Emanuela,et al. HDAC2 negatively regulates memory formation and synaptic plasticity[J]. NATURE,2009,459(7243):55-U58. |
APA | Guan, Ji-Song.,Haggarty, Stephen J..,Giacometti, Emanuela.,Dannenberg, Jan-Hermen.,Joseph, Nadine.,...&Tsai, Li-Huei.(2009).HDAC2 negatively regulates memory formation and synaptic plasticity.NATURE,459(7243),55-U58. |
MLA | Guan, Ji-Song,et al."HDAC2 negatively regulates memory formation and synaptic plasticity".NATURE 459.7243(2009):55-U58. |
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