年齡增大與記憶力下降之間通常可畫上等號,。但美國一項利用小鼠進行的實驗顯示,，這種記憶力衰退的情況并非不可“扭轉”，增加一種叫做RbAp48的腦蛋白或許能讓老年人再次擁有“年輕”大腦,。
美國哥倫比亞大學醫(yī)學中心研究人員28日在《科學—轉化醫(yī)學》雜志上報告說,，他們從哥倫比亞大學人腦庫中獲得了8個人類大腦，其中有年輕人的也有老年人的,，這些大腦來自那些選擇在死后為科研捐腦的人,。經(jīng)對比研究，他們在腦記憶中心海馬區(qū)中找到17個在老年人腦中不能正常工作的基因,，這些基因都位于海馬區(qū)中一個叫齒狀回的區(qū)域,。
進一步研究發(fā)現(xiàn)，在這17個基因中,，受到衰老影響最嚴重的基因是RbAp48,。該基因的表達以及由該基因產(chǎn)生的RbAp48蛋白量在老年人大腦的齒狀回中減少了幾乎一半。
為弄清楚RbAp48對記憶力的影響,，研究人員開展了小鼠試驗,，結果發(fā)現(xiàn)，在年輕小鼠中“關閉”該蛋白會導致它們健忘,，而在老年小鼠中增加該蛋白則恢復了它們的記憶,。論文第一作者、哥倫比亞大學助理研究科學家埃利亞斯·帕夫洛普洛斯說：“增加蛋白不僅改善了小鼠在記憶力測試中的表現(xiàn),，而且其表現(xiàn)可與年輕小鼠相媲美,，這讓我們大吃一驚,。”
這項成果表明，老年人中的記憶力衰退可能是因為腦中RbAp48蛋白含量低下所致,，而這一過程是“可逆的”,，增加該蛋白或可“扭轉”老年人的記憶問題，以此蛋白為標靶將來也許能開發(fā)出新療法,。（生物谷 Bioon.com）
生物谷推薦的英文摘要
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006373
Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48
Elias Pavlopoulos1,2,3, Sidonie Jones4,5,*, Stylianos Kosmidis1,2,3,*, Maggie Close1, Carla Kim1, Olga Kovalerchik1, Scott A. Small4,5,† and Eric R. Kandel1,2,3,†
To distinguish age-related memory loss more explicitly from Alzheimer’s disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention.
