法国科研人员最新发现，随着年纪增长，大脑中的早老蛋白－1的数量会随之增加，从而对老年人的记忆力造成损害。
参与这项研究的法国国家科研中心的亚历山德拉·奥弗雷表示，他们是在研究早期阿尔茨海默氏症时注意到这一现象的。科研人员向实验鼠注射了没有发生基因突变的早老蛋白－1，结果发现，当老鼠脑内出现过量的早老蛋白－1时，大脑中的“突触可塑性”就会出现异常，从而影响到记忆力。
突触是大脑内部信息交换和储存的重要场所，它们构成了神经连接网络。所谓“突触可塑性”指的是这一神经网络的可变和顺应能力，对大脑的记忆力发挥着重要作用。
奥弗雷说，这一研究结果说明，早老蛋白－1对神经具有损害作用。此外，近期的一些研究证实，无论老年人是否患上了阿尔茨海默氏症，他们脑中早老蛋白－1的数量都会有所增长，这就说明该蛋白质会对所有老年人的记忆力产生影响。
这项研究成果已经刊登在美国最新一期《神经学杂志》上。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
