美國研究人員7月11日公布研究成果稱，他們在動物實驗中發(fā)現(xiàn),，一種與長壽相關(guān)的基因似乎也與實驗鼠記憶及學(xué)習(xí)能力密切相關(guān),。
這一基因名為SIRT1,，在此前的研究中,，它編碼的蛋白酶Sirtuin1已被證明可以通過限制熱量消耗來延緩嚙齒類動物的衰老進(jìn)程。
在最新研究中,，由麻省理工學(xué)院大腦和認(rèn)知科學(xué)系教授蔡立慧領(lǐng)導(dǎo)的研究小組利用轉(zhuǎn)基因工程剔除了實驗鼠的SIRT1基因,。在與正常實驗鼠對比時，研究人員發(fā)現(xiàn),，體內(nèi)缺乏SIRT1基因的實驗鼠大腦海馬區(qū)對電流刺激反應(yīng)很差,，而海馬區(qū)是大腦學(xué)習(xí)和長期記憶的關(guān)鍵區(qū)域，在阿爾茨海默氏癥患者中,，海馬區(qū)是首先受損的大腦區(qū)域之一。研究人員還發(fā)現(xiàn),，轉(zhuǎn)基因?qū)嶒炇笊窠?jīng)元密度也有所下降,，后者是衡量大腦活性的重要指標(biāo)。此外,，它們在記憶測試中,，對新舊物體的區(qū)分也不及正常實驗鼠。
蔡立慧說：“這一結(jié)果顯示了SIRT1在大腦中扮演的多重作用,，同時表明它在治療認(rèn)知障礙疾病時具有作為靶向的潛力,。”
蔡立慧表示，這一成果僅是初步性的,，現(xiàn)在利用該成果設(shè)計臨床試驗為時尚早,，但它的確為開發(fā)治療阿爾茨海默氏癥及其他神經(jīng)退行性疾病的藥物提供了方向。
這項研究成果11日發(fā)表在英國《自然》（Nature）雜志上,。(生物谷Bioon.net)
生物谷推薦原文出處：
Nature doi:10.1038/nature09271
A novel pathway regulates memory and plasticity via SIRT1 and miR-134
Jun Gao1,2,3,5, Wen-Yuan Wang1,2,5, Ying-Wei Mao1,2, Johannes Gr?ff1,4, Ji-Song Guan1,2, Ling Pan1,2, Gloria Mak1,2, Dohoon Kim1,2,6, Susan C. Su1,2 & Li-Huei Tsai1,2,4
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Model Animal Research Center, MOE Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing 210061, China
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts 02142, USA
These authors contributed equally to this work.
Present address: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies1, 2. Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown microRNA-based mechanism by which SIRT1 regulates these processes. Furthermore, these results describe a separate branch of SIRT1 signalling, in which SIRT1 has a direct role in regulating normal brain function in a manner that is disparate from its cell survival functions, demonstrating its value as a potential therapeutic target for the treatment of central nervous system disorders.
