一組神經(jīng)學(xué)家最近發(fā)現(xiàn)。大腦利用一種和在胚胎期調(diào)整基因完全相同的機制來保存某些記憶,。Courtney Miller和David Sweatt將他們的這一重要發(fā)現(xiàn)發(fā)表在3月15日的Cell出版社的刊物《Neuron》上,。
研究主要針對一種稱為DNA甲基化的過程對記憶形成的影響，在這一過程中,，甲基分子會和基因結(jié)合然后將它們關(guān)閉,。因此，缺少甲基會保持基因處于激活狀態(tài),。在胚胎時期,，細(xì)胞利用甲基選擇性的關(guān)閉基因，從而使細(xì)胞發(fā)育成各種具體的身體組織,。
甲基化過程會永久的改變基因的狀態(tài)，因此,，當(dāng)Sweatt在之前的研究中發(fā)現(xiàn)這一機制在成年人體內(nèi)同樣存在的時候,，他們開始懷疑甲基同樣是長期記憶形成的機制。但是由于在某些精神病患者體內(nèi)會發(fā)生DNA甲基化,，所以Miller和Sweatt進(jìn)行了相關(guān)實驗進(jìn)行驗證,。
在實驗中，科學(xué)家對處于小室中的老鼠進(jìn)行了適度的電擊,，然后觀察它們是否能產(chǎn)生相關(guān)的記憶,。利用一種阻斷甲基的藥物，小組發(fā)現(xiàn)甲基對于老鼠產(chǎn)生記憶非常重要,。而且科學(xué)家還發(fā)現(xiàn)甲基的濃度直接控制和記憶形成相關(guān)的基因的狀態(tài),。
更重要的是，小組發(fā)現(xiàn)某些異常的甲基化過程和癌癥,、某些孤獨癥以及精神分裂癥有關(guān),。所以這一研究對于了解這些疾病也很有幫助。而且,，在文章中作者們還指出：“我們的發(fā)現(xiàn)顯示出DNA甲基化在行為變化中的動態(tài)調(diào)整是由于對外界環(huán)境刺激的感知帶來,。”
譯自：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
