O'Leary T P, Robertson A, Chipman P H, Rafuse V F, Brown R E
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
Department of Medical Neuroscience, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
Behav Brain Res. 2018 Jan 30;337:256-263. doi: 10.1016/j.bbr.2017.09.009. Epub 2017 Sep 7.
Motor problems occur early in some patients with Alzheimer's disease (AD) and as the disease progresses many patients develop motor dysfunction. Motor dysfunction has been reported in some mouse models of AD, including the 5xFAD mouse, thus this model may be particularly useful for studying motor dysfunction in AD. In order to determine the extent of motor dysfunction in these mice, we tested 11-13 month old female 5xFAD and wildtype (WT) control mice in a battery of motor behaviour tasks. The 5xFAD mice showed hind limb clasping, weighed less and had slower righting reflexes than WT mice. In the open field, the 5xFAD mice travelled a shorter distance than the WT mice, spent less time moving and had a slower movement speed. The 5xFAD mice fell faster than the WT mice from the balance beam, wire suspension, grid suspension and rotarod tasks, indicating dysfunctions in balance, grip strength, motor co-ordination and motor learning. The 5xFAD mice had a short, shuffling gait with a shorter stride length than WT mice and had a slower swim speed. The 5xFAD mice also failed to show an acoustic startle response, likely due to motor dysfunction and previously reported hearing impairment. The 5xFAD mice did not show deficits in the ability of peripheral motor nerves to drive muscle output, suggesting that motor impairments are not due to dysfunction in peripheral motor nerves. These results indicate that the aged 5xFAD mice are deficient in numerous motor behaviours, and suggest that these mice may prove to be a good model for studying the mechanisms of motor dysfunction in AD, and motor behaviour might prove useful for assessing the efficacy of AD therapeutics. Motor dysfunction in 5xFAD mice must also be considered in behavioural tests of sensory and cognitive function so that performance is not confounded by impaired locomotor or swimming behaviour.
运动问题在一些阿尔茨海默病（AD）患者中出现得较早，并且随着疾病进展，许多患者会出现运动功能障碍。在一些AD小鼠模型中已报道存在运动功能障碍，包括5xFAD小鼠，因此该模型可能对研究AD中的运动功能障碍特别有用。为了确定这些小鼠运动功能障碍的程度，我们在一系列运动行为任务中测试了11 - 13月龄的雌性5xFAD小鼠和野生型（WT）对照小鼠。5xFAD小鼠表现出后肢紧握，体重较轻，与WT小鼠相比翻正反射较慢。在旷场实验中，5xFAD小鼠行进的距离比WT小鼠短，移动时间较少且移动速度较慢。在平衡木、悬线、网格悬吊和转棒实验中，5xFAD小鼠比WT小鼠更快掉落，表明在平衡、握力、运动协调和运动学习方面存在功能障碍。5xFAD小鼠步态短小、拖着脚走，步幅比WT小鼠短，游泳速度也较慢。5xFAD小鼠也未表现出听觉惊吓反应，可能是由于运动功能障碍以及先前报道的听力损害。5xFAD小鼠在外周运动神经驱动肌肉输出的能力方面未表现出缺陷，这表明运动障碍并非由于外周运动神经功能障碍所致。这些结果表明，老龄5xFAD小鼠在多种运动行为方面存在缺陷，并表明这些小鼠可能被证明是研究AD中运动功能障碍机制的良好模型，并且运动行为可能对评估对评估AD治疗药物的疗效有用。在感觉和认知功能的行为测试中也必须考虑5xFAD小鼠的运动功能障碍，以便表现不会因运动或游泳行为受损而混淆。
