法國(guó)科研人員最新發(fā)現(xiàn)，隨著年紀(jì)增長(zhǎng),，大腦中的早老蛋白－1的數(shù)量會(huì)隨之增加,，從而對(duì)老年人的記憶力造成損害。
參與這項(xiàng)研究的法國(guó)國(guó)家科研中心的亞歷山德拉·奧弗雷表示,，他們是在研究早期阿爾茨海默氏癥時(shí)注意到這一現(xiàn)象的,。科研人員向?qū)嶒?yàn)鼠注射了沒有發(fā)生基因突變的早老蛋白－1,，結(jié)果發(fā)現(xiàn),，當(dāng)老鼠腦內(nèi)出現(xiàn)過量的早老蛋白－1時(shí)，大腦中的“突觸可塑性”就會(huì)出現(xiàn)異常,，從而影響到記憶力,。
突觸是大腦內(nèi)部信息交換和儲(chǔ)存的重要場(chǎng)所，它們構(gòu)成了神經(jīng)連接網(wǎng)絡(luò),。所謂“突觸可塑性”指的是這一神經(jīng)網(wǎng)絡(luò)的可變和順應(yīng)能力,，對(duì)大腦的記憶力發(fā)揮著重要作用。
奧弗雷說,，這一研究結(jié)果說明,，早老蛋白－1對(duì)神經(jīng)具有損害作用。此外,，近期的一些研究證實(shí),，無論老年人是否患上了阿爾茨海默氏癥，他們腦中早老蛋白－1的數(shù)量都會(huì)有所增長(zhǎng),，這就說明該蛋白質(zhì)會(huì)對(duì)所有老年人的記憶力產(chǎn)生影響,。
這項(xiàng)研究成果已經(jīng)刊登在美國(guó)最新一期《神經(jīng)學(xué)雜志》上。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Neuroscience, August 12, 2009, 29(32):10144-10152; doi:10.1523/JNEUROSCI.1856-09.2009
Age-Dependent Impairment of Spine Morphology and Synaptic Plasticity in Hippocampal CA1 Neurons of a Presenilin 1 Transgenic Mouse Model of Alzheimer's Disease
Alexandra Auffret,1 Vanessa Gautheron,1 Mariaelena Repici,1 Rudolf Kraftsik,2 Howard T. J. Mount,3 Jean Mariani,1,4 and Catherine Rovira1
1Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche (UMR) 7102-Neurobiologie des Processus Adaptatifs (NPA), Centre National de la Recherche Scientifique, UMR 7102-NPA, Paris F-75005, France, 2Department of Cell Biology and Morphology, University of Lausanne, 1005 Lausanne, Switzerland, 3Department of Medicine, Division of Neurology, Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H2, Canada, and 4Assistance Publique–H?pitaux de Paris H?pital Charles Foix, Unité d'Explorations Fonctionnelles, Ivry sur Seine F-94200, France
Presenilin 1 (PS1) mutations are responsible for a majority of early onset familial Alzheimer's disease (FAD) cases, in part by increasing the production of Aβ peptides. However, emerging evidence suggests other possible effects of PS1 on synaptic dysfunction where PS1 might contribute to the pathology independent of Aβ. We chose to study the L286V mutation, an aggressive FAD mutation which has never been analyzed at the electrophysiological and morphological levels. In addition, we analyzed for the first time the long term effects of wild-type human PS1 overexpression. We investigated the consequences of the overexpression of either wild-type human PS1 (hPS1) or the L286V mutated PS1 variant (mutPS1) on synaptic functions by analyzing synaptic plasticity and associated spine density changes from 3 to 15 months of age. We found that mutPS1 induces a transient increase observed only in 4- to 5-month-old mutPS1 animals in NMDA receptor (NMDA-R)-mediated responses and LTP compared with hPS1 mice and nontransgenic littermates. The increase in synaptic functions is concomitant with an increase in spine density. With increasing age, however, we found that the overexpression of human wild-type PS1 progressively decreased NMDA-R-mediated synaptic transmission and LTP, without neurodegeneration. These results identify for the first time a transient increase in synaptic function associated with L286V mutated PS1 variant in an age-dependent manner. In addition, they support the view that the PS1 overexpression promotes synaptic dysfunction in an Aβ-independent manner and underline the crucial role of PS1 during both normal and pathological aging.
