Dept. of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, USA.
Dept. of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS, USA; Dept. of Pharmacology and Toxicology, College of Pharmacy; University of Utah, Salt Lake City UT, USA.
J Neurosci Methods. 2017 Dec 1;292:37-44. doi: 10.1016/j.jneumeth.2017.01.009. Epub 2017 Jan 15.
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and phonic tics. While TS patients have been also shown to exhibit subtle abnormalities of sensorimotor integration and gait, animal models of this disorder are seldom tested for these functions. To fill this gap, we assessed gait and sensorimotor integration in the D1CT-7 mouse, one of the best-validated animal models of TS. D1CT-7 mice exhibit spontaneous tic-like manifestations, which, in line with the clinical phenomenology of TS, are markedly exacerbated by environmental stress. Thus, to verify whether stress may affect sensorimotor integration and gait functions in D1CT-7 mice, we subjected these animals to a 20-min session of spatial confinement, an environmental stressor that was recently shown to worsen tic-like manifestations. Immediately following this manipulation (or no confinement, for controls), animals were subjected to either the sticky-tape task, to test for sensorimotor integration; or a 60-min session in an open field (42×42cm) force-plate actometer for gait analysis. Gait analyses included spatial, temporal, and dynamic (force) parameters. D1CT-7 mice displayed a longer latency to remove a sticky tape, indicating marked impairments in sensorimotor integration; furthermore, these mutants exhibited shortened stride length, increased stride rate, nearly equal early-phase velocity, and higher late-phase velocity. D1CT-7 mice also ran with greater force amplitude than wild-type (WT) littermates. None of these phenotypes was worsened by spatial confinement. These results highlight the potential importance of testing sensorimotor integration and gait functions as a phenotypic correlate of cortical connectivity deficits in animal models of TS.
妥瑞氏症候群（TS）是一种神经发育障碍，其特征是多种运动性和发声性抽搐。虽然已有研究表明 TS 患者的感觉运动整合和步态存在细微异常，但针对该疾病的动物模型很少对此类功能进行测试。为了填补这一空白，我们评估了 D1CT-7 小鼠的步态和感觉运动整合功能，该小鼠是 TS 的最佳验证动物模型之一。D1CT-7 小鼠表现出自发性抽搐样表现，这与 TS 的临床表型一致，并且明显受到环境压力的加剧。因此，为了验证环境压力是否会影响 D1CT-7 小鼠的感觉运动整合和步态功能，我们将这些动物置于 20 分钟的空间限制环境中，这是一种最近被证明会加重抽搐样表现的环境应激源。在这种操作后立即（或没有限制，作为对照），动物进行粘性胶带任务，以测试感觉运动整合；或在开放场（42×42cm）力板测功计中进行 60 分钟的步态分析。步态分析包括空间、时间和动态（力）参数。D1CT-7 小鼠去除粘性胶带的潜伏期更长，表明感觉运动整合明显受损；此外，这些突变体的步幅长度缩短，步频增加，早期速度几乎相等，后期速度更高。D1CT-7 小鼠的力幅值也高于野生型（WT）同窝仔鼠。空间限制没有使这些表型恶化。这些结果强调了测试感觉运动整合和步态功能作为 TS 动物模型皮质连接缺陷的表型相关性的重要性。
