Analysis of Motor Function in the Tg4-42 Mouse Model of Alzheimer’s Disease
Analysis of Motor Function in the Tg4-42 Mouse Model of Alzheimer’s Disease
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阿尔茨海默病 Tg4-42 小鼠模型运动功能分析
DOI：
10.3389/fnbeh.2019.00107
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发表时间：
2019
影响因子：
3
通讯作者：
Y. Bouter
中科院分区：
文献类型：
--
作者：
Jannek M. Wagner;M. Sichler;E. M. Schleicher;T. Franke;C. Irwin;M. Löw;N. Beindorff;C. Bouter;T. Bayer;Y. Bouter
阿尔茨海默病(AD)是一种神经退行性疾病，也是痴呆症最常见的形式。阿尔茨海默病的特点是记忆障碍和认知障碍，但非认知障碍，特别是运动功能障碍也与疾病有关，甚至可能先于典型的临床症状。随着老龄化社会和老年人住院人数的增加，运动障碍成为改善日常生活中独立活动的主要兴趣。与临床结果一致的是，各种AD小鼠模型也会出现运动障碍。我们研究了3个月和7个月大的TG4-42小鼠的运动功能，并与野生型对照组和5XFAD小鼠进行了比较，并结合其他几种AD小鼠模型对结果进行了讨论。我们的研究表明，在平衡木和旋转棒测试中，老年TG4-42小鼠的平衡和运动协调性受到损害，而7个月时一般运动活动和肌肉力量没有受到损害。通过练习，小脑在调节和协调平衡和运动方面发挥着重要作用。特别是，旋转棒测试能够检测出小脑缺陷。此外，18F-FDGPET/MRI证实了假设的小脑损伤。老年TG4-42小鼠在18F-FDG PET中显示小脑葡萄糖代谢降低。这表明，协调和平衡方面的缺陷很可能是由于小脑损伤造成的。总而言之，TG4-42小鼠在记忆障碍之前就出现了运动障碍，没有混淆记忆测试。因此，使TG4-42小鼠模型成为研究针对运动障碍的治疗对认知能力下降的影响的良好模型。
Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia. Hallmarks of AD are memory impairments and cognitive deficits, but non-cognitive impairments, especially motor dysfunctions are also associated with the disease and may even precede classic clinical symptoms. With an aging society and increasing hospitalization of the elderly, motor deficits are of major interest to improve independent activities in daily living. Consistent with clinical findings, a variety of AD mouse models develop motor deficits as well. We investigated the motor function of 3- and 7-month-old Tg4-42 mice in comparison to wild-type controls and 5XFAD mice and discuss the results in context with several other AD mouse model. Our study shows impaired balance and motor coordination in aged Tg4-42 mice in the balance beam and rotarod test, while general locomotor activity and muscle strength is not impaired at 7 months. The cerebellum is a major player in the regulation and coordination of balance and locomotion through practice. Particularly, the rotarod test is able to detect cerebellar deficits. Furthermore, supposed cerebellar impairment was verified by 18F-FDG PET/MRI. Aged Tg4-42 mice showed reduced cerebellar glucose metabolism in the 18F-FDG PET. Suggesting that, deficits in coordination and balance are most likely due to cerebellar impairment. In conclusion, Tg4-42 mice develop motor deficits before memory deficits, without confounding memory test. Thus, making the Tg4-42 mouse model a good model to study the effects on cognitive decline of therapies targeting motor impairments.
影响因子：
1.2
作者：
Seibenhener, Michael L.;Wooten, Michael C.
通讯作者：
Wooten, Michael C.
阿尔茨海默病帕金森病的进展和认知功能丧失。
影响因子：
--
作者：
Wilson,RS;Bennett,DA;Gilley,DW;Beckett,LA;Schneider,JA;Evans,DA
通讯作者：
Evans,DA