文章基本信息

标题：GluN2B subunit-containing NMDA receptor antagonists prevent Aβ-mediated synaptic plasticity disruption in vivo
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作者：Neng-Wei Hu ; Igor Klyubin ; Roger Anwyl 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：48
页码：20504-20509
DOI：10.1073/pnas.0908083106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Currently, treatment with the relatively low-affinity NMDA receptor antagonist memantine provides limited benefit in Alzheimer's disease (AD). One probable dose-limiting factor in the use of memantine is the inhibition of NMDA receptor-dependent synaptic plasticity mechanisms believed to underlie certain forms of memory. Moreover, amyloid-{beta} protein (A{beta}) oligomers that are implicated in causing the cognitive deficits of AD potently inhibit this form of plasticity. Here we examined if subtype-preferring NMDA receptor antagonists could preferentially protect against the inhibition of NMDA receptor-dependent plasticity of excitatory synaptic transmission by A{beta} in the hippocampus in vivo. Using doses that did not affect control plasticity, antagonists selective for NMDA receptors containing GluN2B but not other GluN2 subunits prevented A{beta}1-42 -mediated inhibition of plasticity. Evidence that the proinflammatory cytokine TNF{alpha} mediates this deleterious action of A{beta} was provided by the ability of TNF{alpha} antagonists to prevent A{beta}1-42 inhibition of plasticity and the abrogation of a similar disruptive effect of TNF{alpha} using a GluN2B-selective antagonist. Moreover, at nearby synapses that were resistant to the inhibitory effect of TNF{alpha
关键词：Alzheimer's disease ; amyloid-β protein oligomers ; glutamate