Neuron：研究发现使大脑的某些记忆保留一生的机制
一组神经学家最近发现。大脑利用一种和在胚胎期调整基因完全相同的机制来保存某些记忆。Courtney Miller和David Sweatt将他们的这一重要发现发表在3月15日的Cell出版社的刊物《Neuron》上。
研究主要针对一种称为DNA甲基化的过程对记忆形成的影响，在这一过程中，甲基分子会和基因结合然后将它们关闭。因此，缺少甲基会保持基因处于激活状态。在胚胎时期，细胞利用甲基选择性的关闭基因，从而使细胞发育成各种具体的身体组织。
甲基化过程会永久的改变基因的状态，因此，当Sweatt在之前的研究中发现这一机制在成年人体内同样存在的时候，他们开始怀疑甲基同样是长期记忆形成的机制。但是由于在某些精神病患者体内会发生DNA甲基化，所以Miller和Sweatt进行了相关实验进行验证。
在实验中，科学家对处于小室中的老鼠进行了适度的电击，然后观察它们是否能产生相关的记忆。利用一种阻断甲基的药物，小组发现甲基对于老鼠产生记忆非常重要。而且科学家还发现甲基的浓度直接控制和记忆形成相关的基因的状态。
更重要的是，小组发现某些异常的甲基化过程和癌症、某些孤独症以及精神分裂症有关。所以这一研究对于了解这些疾病也很有帮助。而且，在文章中作者们还指出：“我们的发现显示出DNA甲基化在行为变化中的动态调整是由于对外界环境刺激的感知带来。”
译自：physorg.com
部分英文原文：
Neuron, Volume 53, Issue 6 , 15 March 2007, Pages 857-869
Covalent Modification of DNA Regulates Memory Formation
Courtney A. Miller1 and J. David Sweatt1,
1Department of Neurobiology and the Evelyn F. McKnight Brain Institute,University of Alabama at Birmingham, Birmingham, AL 35294, USA
Received 2 October 2006; revised 6 January 2007; accepted 26 February 2007. Published: March 14, 2007. Available online 14 March 2007.
Summary
DNA methylation is a covalent chemical modification of DNA catalyzed by DNA methyltransferases (DNMTs). DNA methylation is associated with transcriptional silencing and has been studied extensively as a lifelong molecular information storage mechanism put in place during development. Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation. In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation. DNMT inhibition prevents the PP1 methylation increase, resulting in aberrant transcription of the gene during the memory-consolidation period. These results demonstrate that DNA methylation is dynamically regulated in the adult nervous system and that this cellular mechanism is a crucial step in memory formation.
Author Keywords: MOLNEURO; SIGNALING; HUMDISEASE
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