Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Brain Res. 2021 Jul 1;1762:147437. doi: 10.1016/j.brainres.2021.147437. Epub 2021 Mar 19.
The triple transgenic Alzheimer's disease (3xTg-AD) strain is a common mouse model used for studying the pathology and mechanism of Alzheimer's disease (AD). The 3xTg-AD strain exhibits two hallmarks of AD, amyloid beta (Aβ) and neurofibrillary tangles. Several studies using different gender and age of 3xTg-AD mice to investigate their behavior phenotypes under the influence of various treatments have reported mixed results. Therefore, a comprehensive investigation on the optimal gender, age, and training paradigms used for behavioral studies of 3xTg-AD is necessary. In the present study, we investigated the behavioral phenotypes for the two genders of 3xTg-AD mice at 3, 6, 9, and 12 months old and compared the results with age-, gender-matched C57BL/6N control strain. All mice were subjected to tail flick, pinprick, open field, elevated plus maze, passive avoidance, and trace fear conditioning (TFC) tests to evaluate their sensory, locomotor, anxiety, and learning/memory functions. The results showed that TFC on male 3xTg-AD mice is optimal for studying the memory performance in AD. The sensory and locomotor functions of 3xTg-AD mice for two genders appear to be normal before 6 months, decline in fear memory afterwards. The differences between control and 3xTg-AD male mice in contextual and cued memory are robust, thus they are ideal for evaluating the effect of a treatment. Since it is costly and time consuming to obtain wildtype littermates as controls, C57BL/6N strain is suggested to be used as control mice because their baseline performance of sensorimotor functions are similar to that of 3xTg-AD mice.
三重转基因阿尔茨海默病（3xTg-AD）品系是一种常用的小鼠模型，用于研究阿尔茨海默病（AD）的病理学和发病机制。3xTg-AD 品系表现出 AD 的两个特征，即淀粉样β（Aβ）和神经原纤维缠结。一些使用不同性别和年龄的 3xTg-AD 小鼠的研究，在不同的处理影响下，调查它们的行为表型，报告的结果存在差异。因此，需要对 3xTg-AD 进行全面的研究，以确定用于行为研究的最佳性别、年龄和训练方案。在本研究中，我们调查了 3、6、9 和 12 个月大的 3xTg-AD 雌雄小鼠的行为表型，并将结果与年龄、性别匹配的 C57BL/6N 对照品系进行了比较。所有小鼠均接受尾部敲击、刺痛、旷场、高架十字迷宫、被动回避和痕迹恐惧条件反射（TFC）测试，以评估它们的感觉、运动、焦虑和学习/记忆功能。结果表明，雄性 3xTg-AD 小鼠的 TFC 最适合研究 AD 的记忆表现。在 6 个月之前，雌雄 3xTg-AD 小鼠的感觉和运动功能似乎正常，之后恐惧记忆下降。雄性对照和 3xTg-AD 小鼠在情景和线索记忆之间的差异明显，因此它们是评估治疗效果的理想模型。由于获得野生型同窝仔作为对照既昂贵又耗时，建议使用 C57BL/6N 品系作为对照小鼠，因为它们的感觉运动功能基线表现与 3xTg-AD 小鼠相似。
