Skillings Elizabeth A, Wood Nigel I, Morton A Jennifer
Department of Physiology, Development and Neuroscience, University of Cambridge Cambridge, CB2 3DY, UK.
Brain Behav. 2014 Sep;4(5):675-86. doi: 10.1002/brb3.235. Epub 2014 Jul 17.
In addition to their cognitive and motor deficits, R6/2 mice show a progressive disintegration in circadian rhythms that mirrors the problems associated with sleep-wake disturbances experienced by patients with Huntington's disease (HD). It has been shown previously that motor and cognitive performance, as well as survival, can be improved in transgenic mouse models of HD through the provision of environmental enrichment.
We compared the effect of two different overnight entrainment paradigms presented either separately or in combination. The first was environmental enrichment, the second was temporal food-entrainment. Environmental enrichment was provided in the dark period (the natural active period for mice) in the form of access to a Perspex playground containing running wheels, tunnels, climbing frame, ropes and chew blocks. Food entrainment was imposed by allowing access to food only during the dark period. We assessed a number of different aspects of function in the mice, measuring general health (by SHIRPA testing, body temperature and body weight measurements), cognitive performance in the touchscreen and locomotor behavior in the open field.
There were no significant differences in cognitive performance between groups on different schedules. Environmental enrichment delayed the onset of general health deterioration, while food entrainment slowed the loss of body weight, aided the maintenance of body temperature and improved locomotor behavior. Effects were limited however, and in combination had deleterious effects on survival.
Our results support previous studies showing that environmental enrichment can be beneficial and might be used to enhance the quality of life of HD patients. However, improvements are selective and 'enrichment' per se is likely to only be useful as an adjunct to a more direct therapy.
除了认知和运动缺陷外，R6/2小鼠的昼夜节律也在逐渐瓦解，这反映了亨廷顿舞蹈症（HD）患者所经历的与睡眠-觉醒障碍相关的问题。先前的研究表明，通过提供环境富集，HD转基因小鼠模型的运动和认知能力以及生存率都可以得到改善。
我们比较了两种不同的过夜同步范式单独或联合呈现的效果。第一种是环境富集，第二种是限时进食同步。在黑暗期（小鼠的自然活跃期）以进入含有跑步轮、隧道、攀爬架、绳索和咀嚼块的有机玻璃游乐场的形式提供环境富集。通过仅在黑暗期允许获取食物来实施限时进食同步。我们评估了小鼠功能的多个不同方面，测量了一般健康状况（通过SHIRPA测试、体温和体重测量）、触屏上的认知表现以及旷场中的运动行为。
不同时间表组之间的认知表现没有显著差异。环境富集延迟了一般健康状况恶化的 onset，而限时进食减缓了体重减轻，有助于维持体温并改善运动行为。然而，效果有限，并且联合使用对生存率有有害影响。
我们的结果支持先前的研究，表明环境富集可能有益，并且可用于提高HD患者的生活质量。然而，改善是有选择性的，并且“富集”本身可能仅作为更直接治疗的辅助手段才有用。
