Aβ oligomers inhibit synapse remodelling necessary for memory consolidation.
Aβ oligomers inhibit synapse remodelling necessary for memory consolidation.
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DOI：
10.1016/j.neurobiolaging.2010.01.001
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发表时间：
2011-12
影响因子：
4.2
通讯作者：
Regan, Ciaran M.
中科院分区：
文献类型：
--
作者：
Freir, Darragh B.;Fedriani, Rocio;Scully, Darren;Smith, Imelda M.;Selkoe, Dennis J.;Walsh, Dominic M.;Regan, Ciaran M.
广泛的研究表明，淀粉样β蛋白（Aβ）与阿尔茨海默病（AD）的发病有关。这种蛋白质已被证明在注射到啮齿动物大脑中时会产生记忆缺陷，并且在AD Aβ产生的小鼠模型中与学习和/或回忆受损相关。在这里，我们研究了细胞来源的SDS稳定的7 PA 2来源的可溶性Aβ寡聚体对巩固回避学习的影响。在训练后0、3、6、9或12 h，动物接受侧脑室注射含Aβ或对照培养基，并在24和48 h进行回忆测试。在48小时回忆后，立即对动物进行经心灌注，并取出脑进行切片和EM分析。在训练后6或9 h接受Aβ注射的大鼠在48 h表现出记忆巩固的显著损害。重要的是，在9小时注射的受损动物在齿状回中的突触显著减少。这些数据表明，Aβ低n寡聚体靶向巩固相关突触重塑的特定时间方面，从而功能性突触的丧失导致巩固受损。
Extensive research has implicated the amyloid-β protein (Aβ) in the aetiology of Alzheimer’s disease (AD). This protein has been shown to produce memory deficits when injected into rodent brain and in mouse models of AD Aβ production is associated with impaired learning and/or recall. Here we examined the effects of cell-derived SDS-stable 7PA2-derived soluble Aβ oligomers on consolidation of avoidance learning. At 0, 3, 6, 9 or 12 h after training, animals received an intracerebroventricular injection of Aβ-containing or control media and recall was tested at 24 and 48 h. Immediately after 48 h recall animals were transcardially perfused and the brain removed for sectioning and EM analysis. Rats receiving injections of Aβ at 6 or 9 h post-training showed a significant impairment in memory consolidation at 48 h. Importantly, impaired animals injected at 9 h had significantly fewer synapses in the dentate gyrus. These data suggest that Aβ low-n oligomers target specific temporal facets of consolidation-associated synaptic remodelling whereby loss of functional synapses results in impaired consolidation.
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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：
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影响因子：
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DOI：
10.1073/pnas.95.11.6448
发表时间：
1998-05-26
影响因子：
11.1
作者：
Lambert, MP;Barlow, AK;Klein, WL
通讯作者：
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影响因子：
168.9
作者：
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