記憶的形成是一個(gè)相當(dāng)奇妙又神秘的過程,。一直以來，有很多的研究人員致力于破解這個(gè)過程中的一個(gè)又一個(gè)謎團(tuán)?，F(xiàn)在,，蒙特利爾的一個(gè)研究組發(fā)現(xiàn)一種能夠抑制新的信息轉(zhuǎn)化成長(zhǎng)期記憶的蛋白質(zhì)——GCN2可能是將短期記憶變成長(zhǎng)期記憶的一個(gè)主控調(diào)節(jié)因子。他們的研究結(jié)果公布在8月25日的Nature雜志上,。研究首次證明這種蛋白質(zhì)合成對(duì)記憶形成的調(diào)節(jié)至關(guān)重要,。這一新發(fā)現(xiàn)依賴于多個(gè)國家研究人員的通力合作。
Costa-Mattioli說,，不是所有人們獲得的新信息都以長(zhǎng)期記憶的形式被儲(chǔ)存起來,。例如，當(dāng)讓一些人記下書上的一段文字后,，在最初的一段時(shí)間內(nèi)人們能夠背誦出這個(gè)段落,，但是這種記憶并沒有完全儲(chǔ)存在大腦中，因此還需要花費(fèi)更多的時(shí)間記憶,。
在一系列實(shí)驗(yàn)中，研究人員證明沒有GCN2蛋白的轉(zhuǎn)基因小鼠獲得的新信息沒有像正常小鼠那樣容易“退色”,，即這種新信息更頻繁地被轉(zhuǎn)化成了長(zhǎng)期記憶,。因此，研究人員推測(cè)GCN2可能阻止新信息被儲(chǔ)存成長(zhǎng)期記憶,。
大腦中長(zhǎng)期記憶的形成需要同時(shí)活化便利記憶儲(chǔ)存的分子和沉默像GCN2這樣抑制記憶儲(chǔ)存的蛋白質(zhì),。盡管目前離進(jìn)行人類試驗(yàn)還相當(dāng)遙遠(yuǎn)，但是研究人員相信他們的發(fā)現(xiàn)將可能為各種與記憶有關(guān)的疾病提供一種治療方法,。GCN2蛋白在長(zhǎng)期記憶形成中功能的發(fā)現(xiàn)將可能幫助研究人員開發(fā)出提高記憶力喪失的病人提高記憶力,。
Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins1, 2. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2-/- mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2-/- slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2-/- mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2-/- mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway
原文：
Translational control of hippocampal synaptic plasticity and memory by the eIF2 kinase GCN2, Nature 436, 1166-1173 (25 August 2005)
原文下載
GCN2基本信息
有關(guān)這個(gè)基因的全部信息：http://db.yeastgenome.org/cgi-bin/singlepageformat?sgdid=S000002691
或：http://www.pdg.cnb.uam.es/UniPub/iHOP/gs/32291.html
GCN2 GO evidence and references
phenotype/phenotype.pl?dbid=S000002691">GCN2 Phenotype details and references
GCN2 All Interactions details and references
有關(guān)作者單位的簡(jiǎn)介：
Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins1, 2. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2-/- mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2-/- slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2-/- mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2-/- mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway
