Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model.
Impairments in remote memory stabilization precede hippocampal synaptic and cognitive failures in 5XFAD Alzheimer mouse model.
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DOI：
10.1016/j.nbd.2008.10.006
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发表时间：
2009-02
影响因子：
6.1
通讯作者：
Ohno M
中科院分区：
文献类型：
--
作者：
Kimura R;Ohno M
虽然阿尔茨海默病（AD）的动物模型重现了β-淀粉样蛋白依赖的海马突触和认知功能障碍，但对初始海马编码后皮层依赖的远程记忆稳定性如何受到影响知之甚少。在这里，我们系统地分析了生物物理和行为表型，包括远程记忆功能，5XFAD APP/PS1转基因小鼠含有5个家族性AD突变。我们发现，5XFAD小鼠表现出海马功能障碍，如通过降低Schaffer侧支-CA 1突触的基线传递和长时程增强水平所观察到的。海马依赖性记忆测试1天后，上下文恐惧条件反射也受损的年龄依赖性在5XFAD小鼠，与海马突触失败的发病。重要的是，在海马功能障碍发作之前，5XFAD小鼠在训练后30天内的远程记忆稳定性显著下降。我们的研究结果表明，5XFAD小鼠提供了一个有用的模型系统，以研究与AD相关的多种突触和记忆功能障碍的机制和治疗干预。
Although animal models of Alzheimer’s disease (AD) recapitulate β-amyloid-dependent hippocampal synaptic and cognitive dysfunctions, it is poorly understood how cortex-dependent remote memory stabilization following initial hippocampal coding is affected. Here, we systematically analyzed biophysical and behavioral phenotypes, including remote memory functions, of 5XFAD APP/PS1 transgenic mice containing five familial AD mutations. We found that 5XFAD mice show hippocampal dysfunctions as observed by reduced levels of baseline transmission and long-term potentiation at Schaffer collateral-CA1 synapses. Hippocampus-dependent memory tested 1 day after contextual fear conditioning was also impaired age-dependently in 5XFAD mice, as correlated with the onset of hippocampal synaptic failures. Importantly, remote memory stabilization during 30 days after training significantly declined in 5XFAD mice at time well before the onset of hippocampal dysfunctions. Our results indicate that 5XFAD mice provide a useful model system to investigate the mechanisms and therapeutic interventions for multiple synaptic and memory dysfunctions associated with AD.
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影响因子：
56.9
作者：
Frankland, PW;Bontempi, B;Silva, AJ
通讯作者：
Silva, AJ
影响因子：
6.1
作者：
Almeida, CG;Tampellini, D;Gouras, GK
通讯作者：
Gouras, GK
影响因子：
5.3
作者：
Fitzjohn, SM;Morton, RA;Seabrook, GR
通讯作者：
Seabrook, GR
DOI：
10.1073/pnas.0600948103
发表时间：
2006-03-28
影响因子：
11.1
作者：
Jacobsen, JS;Wu, CC;Bloom, FE
通讯作者：
Bloom, FE
影响因子：
25
作者：
Chapman, PF;White, GL;Hsiao, KK
通讯作者：
Hsiao, KK