生物谷報道：未成熟大腦具有熟練架構(gòu)自身（神經(jīng)系統(tǒng)）以適應(yīng)生活環(huán)境改變的特性,，這是神經(jīng)生物學(xué)中最令人匪夷所思的一點,。這種特性就是所謂的可塑性,。然而，未成熟大腦的這一奇特可塑性僅見于被稱為臨界期的一段短暫的時間內(nèi),。例如,，兒童在屬于早期臨界期的嬰幼兒階段被剝奪正常視覺刺激，就會患上弱視,，導(dǎo)致永久性的視力缺損,。目前,研究人員通過比較經(jīng)歷視覺體驗的幼鼠和成年鼠大腦的遺傳區(qū)域，已經(jīng)發(fā)現(xiàn)對大腦可塑性可能起關(guān)鍵作用的遺傳活動的差異,。托馬索·彼左魯索和同事在2007年3月1日出版的《神經(jīng)元》雜志（肖爾出版社）上發(fā)表了該研究成果,。
在試驗過程中, 研究人員讓幼鼠和成年鼠在黑暗中生活了3天,，之后每隔一段時間讓其適應(yīng)正常光線,，并對每只鼠的大腦視皮質(zhì)的遺傳區(qū)域反應(yīng)進(jìn)行分析。研究人員發(fā)現(xiàn)幼鼠大腦有特異性遺傳活動,，而成年鼠大腦則沒有,。此外，研究人員還意外發(fā)現(xiàn)這一視覺體驗?zāi)軌虼碳び资蟠竽X里的組蛋白發(fā)生化學(xué)修飾,，而成年鼠則無此發(fā)現(xiàn),。
組蛋白經(jīng)由DNA纏繞，從而形成串珠樣結(jié)構(gòu)的核小體,。組蛋白的化學(xué)修飾使DNA能夠接觸激活基因的區(qū)域,。研究人員同時發(fā)現(xiàn)，受視覺刺激激活的基因能夠調(diào)控其他基因的轉(zhuǎn)錄,。轉(zhuǎn)錄是將DNA基因復(fù)制成RNA的過程,，是制造蛋白的一張藍(lán)圖。為了確定組蛋白的化學(xué)修飾是否對大腦可塑性產(chǎn)生功能上的影響,，研究人員做了一個試驗,，即給予成年鼠服用一種能夠增加組蛋白化學(xué)修飾的藥物,。結(jié)果顯示，成年鼠的視覺可塑性確實有所增加,。
彼左魯索和同事下結(jié)論道：我們的結(jié)果顯示,，視覺體驗可在不同程度上激活幼鼠和成年鼠大腦視皮質(zhì)中調(diào)控基因表達(dá)的胞內(nèi)信號傳導(dǎo)通路，并且這種發(fā)育下調(diào)節(jié)可以下調(diào)節(jié)成年鼠大腦視皮質(zhì)中的可塑性發(fā)育,。神經(jīng)系統(tǒng)的重新架構(gòu)有賴于組蛋白的化學(xué)修飾,，而視覺體驗刺激產(chǎn)生化學(xué)修飾的能力下降與臨界期的終止具有相關(guān)性。同時他們還說道：我們所發(fā)現(xiàn)的這一機(jī)制可能對臨界期的視皮質(zhì)可塑性具有重要意義,，并且臨界期的終止可能與視皮質(zhì)中的下調(diào)節(jié)有關(guān),。因此，產(chǎn)生于臨界期終止階段的可塑性發(fā)育下調(diào)節(jié)可能是由作用于細(xì)胞膜內(nèi),、外的不同水平的多分子機(jī)制所引起,。
Figure 1. Visual Stimulation Induces MSK Thr 581 Phosphorylation
(A) The number of pMSK-positive cells is increased by 15 min of visual stimulation. The activation is transient and returns to baseline at 40 min (dr, n = 7; 15 min, n = 11; 40 min, n = 4; one-way ANOVA, p = 0.003; post hoc Holm-Sidak: 15 min versus dr, p < 0.05; 15 min versus 40 min, p < 0.05; 40 min versus dr, p = 0.53). Hollow symbols represent data from single animals; filled symbols report average ± SEM. Data are normalized to the average of dr animals.
(B) Examples of pMSK staining in visual cortex of dr and 15 min mice. Cortical layers are indicated on the right. The inset shows the nuclear staining of pMSK as shown by a double staining for Neurotrace. Scale bar = 70 μm (10 μm for the inset).
(C) MSK phosphorylation induced by visual stimulation is blocked by inhibition of ERK. Average (±SEM) number of pMSK-positive cells (normalized to the dr value, dotted line) in visual cortex of mice visually stimulated for 15 min and treated with UO126. Significantly fewer positive cells are present in the treated cortex with respect to the contralateral untreated cortex (n = 6, paired t test, p = 0.01). The number of pMSK-positive cells in the cortex treated with the inhibitor vehicle is not different from that in the untreated contralateral cortex (n = 6, paired t test, p = 0.48). On the right, pMSK staining from a mouse visually stimulated for 15 min with one cortex infused with UO126. Scale bar = 60 μm.
(D) pMSK (red) and pERK (green) staining coexist in the same cells. Cells (n = 602) were classified as single-stained for pERK, single-stained for pMSK, or pMSK/pERK double-stained after inspection of z-stacks of confocal images. Scale bar = 14 μm.
原文出處:
Neuron March 1, 2007: 53 (5)
Developmental Downregulation of Histone Posttranslational Modifications Regulates Visual Cortical Plasticity
Elena Putignano, Giuseppina Lonetti, Laura Cancedda, Gianmichele Ratto, Mario Costa, Lamberto Maffei, and Tommaso Pizzorusso
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