A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease.
A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0080355
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bitan G
中科院分区：
文献类型：
--
作者：
Attar A;Liu T;Chan WT;Hayes J;Nejad M;Lei K;Bitan G
阿尔茨海默病是一种进行性神经退行性疾病，表现为记忆丧失、认知功能障碍和痴呆。阿尔茨海默病的动物模型有助于理解潜在的病理机制和评估潜在的治疗方法。AD的三重转基因（3×Tg）小鼠模型是独特的，因为它概括了阿尔茨海默病的病理标志-淀粉样斑块和神经元缠结。在该模型中，大多数组在6月龄时显示出最早的认知缺陷，在开始评价治疗的认知作用之前，需要将小鼠老化至该年龄。为了评估3×Tg小鼠的认知缺陷，最初我们采用了15次训练试验的典型巴恩斯迷宫方案，但在老年小鼠中没有发现显著缺陷。因此，我们缩短了方案，仅包括5个训练试验，以增加难度。我们发现使用该协议的认知缺陷主要使用探测日的测量值，而不是训练试验。这也减少了数据分析的工作量。我们比较了3×Tg和野生型小鼠在4个月和15个月的年龄，使用原始的，长期的训练，和短期的训练模式。我们发现，在第四次训练试验后，3×Tg和野生型小鼠之间的学习差异消失了。在探测日的学习和记忆测量结果显示，3×Tg小鼠和野生型小鼠在短的5次训练试验方案下存在显著差异，但在长的15次训练试验方案下没有显著差异。重要的是，我们使用短Barnes迷宫方案在4个月大的3×Tg小鼠中检测到认知功能障碍。使用缩短的巴恩斯迷宫方案在4-m龄3×Tg小鼠中测试学习和记忆的能力提供了相当多的时间和成本节省，并为在病理学前阶段利用该模型进行治疗研究提供了支持。
Alzheimer's disease is a progressive neurodegenerative disease that manifests as memory loss, cognitive dysfunction, and dementia. Animal models of Alzheimer's disease have been instrumental in understanding the underlying pathological mechanism and in evaluation of potential therapies. The triple transgenic (3×Tg) mouse model of AD is unique because it recapitulates both pathologic hallmarks of Alzheimer's disease - amyloid plaques and neurofibrillary tangles. The earliest cognitive deficits in this model have been shown at 6-m of age by most groups, necessitating aging of the mice to this age before initiating evaluation of the cognitive effects of therapies. To assess cognitive deficits in the 3×Tg mice, originally we employed a typical Barnes maze protocol of 15 training trials, but found no significant deficits in aged mice. Therefore, we shortened the protocol to include only 5 training trials to increase difficulty. We found cognitive deficits using this protocol using mainly measures from the probe day, rather than the training trials. This also decreased the effort involved with data analysis. We compared 3×Tg and wild-type mice at 4-m- and 15-m of age using both the original, long training, and the short training paradigms. We found that differences in learning between 3×Tg and wild-type mice disappeared after the 4th training trial. Measures of learning and memory on the probe day showed significant differences between 3×Tg and wild-type mice following the short, 5-training trial protocol but not the long, 15-training trial protocol. Importantly, we detected cognitive dysfunction already at 4-m of age in 3×Tg mice using the short Barnes-maze protocol. The ability to test learning and memory in 4-m old 3×Tg mice using a shortened Barnes maze protocol offers considerable time and cost savings and provides support for the utilization of this model at pre-pathology stages for therapeutic studies.
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DOI：
10.1016/s1474-4422(12)70227-2
发表时间：
2012-12
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Fleisher AS;Chen K;Quiroz YT;Jakimovich LJ;Gomez MG;Langois CM;Langbaum JB;Ayutyanont N;Roontiva A;Thiyyagura P;Lee W;Mo H;Lopez L;Moreno S;Acosta-Baena N;Giraldo M;Garcia G;Reiman RA;Huentelman MJ;Kosik KS;Tariot PN;Lopera F;Reiman EM
通讯作者：
Reiman EM
影响因子：
4
作者：
Davis, Katherine E.;Easton, Alexander;Gigg, John
通讯作者：
Gigg, John
影响因子：
4.2
作者：
Ambree, Oliver;Richter, Helene;Schaebitz, Wolf-Ruediger
通讯作者：
Schaebitz, Wolf-Ruediger
DOI：
10.1523/jneurosci.0490-10.2010
发表时间：
2010-05-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clinton LK;Blurton-Jones M;Myczek K;Trojanowski JQ;LaFerla FM
通讯作者：
LaFerla FM
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA