HDAC1 Regulates Fear Extinction in Mice
HDAC1 Regulates Fear Extinction in Mice
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DOI：
10.1523/jneurosci.0079-12.2012
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发表时间：
2012-04-11
影响因子：
5.3
通讯作者：
Sananbenesi, Farahnaz
中科院分区：
文献类型：
--
作者：
Bahari-Javan, Sanaz;Maddalena, Andrea;Sananbenesi, Farahnaz
组蛋白乙酰化与神经精神障碍的发病机制有关，使用组蛋白脱乙酰酶(HDAC)抑制剂靶向组蛋白脱乙酰酶(HDAC)被证明具有神经保护作用，并启动神经再生过程。然而，对单个HDAC蛋白在脑部疾病发病机制中的作用知之甚少。研究发现，HDAC1在患有神经精神疾病的患者中表达上调。在这里，我们表明，病毒介导的神经元HDAC1在成年小鼠海马区的过度表达特异性地影响上下文恐惧记忆的消退，而其他认知能力不受影响。在随后的实验中，我们证明在生理条件下，海马区HDAC1需要通过一种涉及H3K9去乙酰化和随后的靶基因三甲基化的机制来进行消亡学习。总而言之，我们的数据表明，海马区HDAC1在记忆功能中具有特定的作用。
Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was found to be upregulated in patients suffering from neuropsychiatric diseases. Here, we show that virus-mediated overexpression of neuronal HDAC1 in the adult mouse hippocampus specifically affects the extinction of contextual fear memories, while other cognitive abilities were unaffected. In subsequent experiments we show that under physiological conditions, hippocampal HDAC1 is required for extinction learning via a mechanism that involves H3K9 deacetylation and subsequent trimethylation of target genes. In conclusion, our data show that hippocampal HDAC1 has a specific role in memory function.