Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.
Natural amyloid-β oligomers acutely impair the formation of a contextual fear memory in mice.
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DOI：
10.1371/journal.pone.0029940
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Reijmers LG
中科院分区：
文献类型：
--
作者：
Kittelberger KA;Piazza F;Tesco G;Reijmers LG
记忆丧失是阿尔茨海默病（AD）的标志性症状之一。有人提出可溶性淀粉样蛋白- β (β)低聚物严重损害神经元功能，从而损害记忆。我们在此报告，天然β低聚物严重损害小鼠的情境恐惧记忆。从7PA2细胞的条件培养基中提取含有Abeta单体、二聚体、三聚体和四聚体的天然Abeta低聚物溶液，7PA2细胞是一种表达含有Val717Phe家族性AD突变的人类淀粉样蛋白前体蛋白的细胞系。作为对照，我们使用7PA2条件培养基，通过免疫去除Abeta低聚物。将两组小鼠分别通过套管注入侧脑室，注射Abeta和对照溶液，并使用两种音调-电击配对进行恐惧调节。在恐惧条件反射后的第二天，在单独的检索试验中测试了小鼠的情境恐惧记忆和音调恐惧记忆。进行了三个实验。在实验1中，小鼠分别在恐惧条件反射前1小时、后3小时和情境检索前1小时注射三次。实验2和实验3分别在恐惧条件反射前1小时和2小时对小鼠进行单次注射。在所有三个实验中，对音调恐惧记忆没有影响。在恐惧条件反射前1小时注射，而不是在恐惧条件反射前2小时注射，破坏了情境恐惧记忆的形成。在未来的研究中，天然β寡聚物对情境恐惧记忆的急性作用可用于确定AD相关记忆丧失的潜在机制和治疗方法。
Memory loss is one of the hallmark symptoms of Alzheimer's disease (AD). It has been proposed that soluble amyloid-beta (Abeta) oligomers acutely impair neuronal function and thereby memory. We here report that natural Abeta oligomers acutely impair contextual fear memory in mice. A natural Abeta oligomer solution containing Abeta monomers, dimers, trimers, and tetramers was derived from the conditioned medium of 7PA2 cells, a cell line that expresses human amyloid precursor protein containing the Val717Phe familial AD mutation. As a control we used 7PA2 conditioned medium from which Abeta oligomers were removed through immunodepletion. Separate groups of mice were injected with Abeta and control solutions through a cannula into the lateral brain ventricle, and subjected to fear conditioning using two tone-shock pairings. One day after fear conditioning, mice were tested for contextual fear memory and tone fear memory in separate retrieval trials. Three experiments were performed. For experiment 1, mice were injected three times: 1 hour before and 3 hours after fear conditioning, and 1 hour before context retrieval. For experiments 2 and 3, mice were injected a single time at 1 hour and 2 hours before fear conditioning respectively. In all three experiments there was no effect on tone fear memory. Injection of Abeta 1 hour before fear conditioning, but not 2 hours before fear conditioning, impaired the formation of a contextual fear memory. In future studies, the acute effect of natural Abeta oligomers on contextual fear memory can be used to identify potential mechanisms and treatments of AD associated memory loss.
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影响因子：
16.2
作者：
Renner, Marianne;Lacor, Pascale N.;Velasco, Pauline T.;Xu, Jian;Contractor, Anis;Klein, William L.;Triller, Antoine
通讯作者：
Triller, Antoine
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：
2.7
作者：
O'Hare, Eugene;Scopes, David I. C.;Kim, Eun-Mee
通讯作者：
Kim, Eun-Mee
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH
影响因子：
4
作者：
Granic, Ivica;Masman, Marcelo F.;Eisel, Ulrich L. M.
通讯作者：
Eisel, Ulrich L. M.