Manfré Giuseppe, Clemensson Erik K H, Kyriakou Elisavet I, Clemensson Laura E, van der Harst Johanneke E, Homberg Judith R, Nguyen Huu Phuc
Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands.
Noldus Information Technology BV, Wageningen, Netherlands.
Front Behav Neurosci. 2017 Nov 3;11:218. doi: 10.3389/fnbeh.2017.00218. eCollection 2017.
: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype. : The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping. : Wild-type (WT) and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance. : BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected. : The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.
亨廷顿舞蹈症（HD）是一种进行性神经退行性疾病，其特征为运动、认知和神经精神症状。HD通常通过运动功能缺陷的出现来诊断，这些缺陷会导致手部熟练使用能力受损、步态异常、肌肉萎缩和舞蹈样动作。HD的BACHD转基因大鼠模型是一种成熟的HD转基因啮齿动物模型，为深入表征运动表型提供了可能。
本研究旨在结合经典范式与新型高通量行为表型分析，对BACHD大鼠运动功能的不同方面进行表征。
对野生型（WT）和转基因动物从2月龄到12月龄进行纵向测试。为测量精细运动控制能力，用意大利面处理测试和颗粒抓取测试对大鼠进行挑战。为评估粗略运动功能，通过握杆测试和握力测试对动物进行评估。在自动饲养笼环境（即PhenoTyper）中评估自发运动活动和昼夜节律性。然后，我们将现有的经典运动功能测试方法与自动饲养笼运动性能评估相结合。
BACHD大鼠在2月龄时肌肉耐力出现严重受损。在转基因动物中观察到昼夜节律性和运动活动的改变。另一方面，抓取行为、前爪灵活性和肌肉力量未受影响。
BACHD大鼠模型表现出HD患者的某些特征，如肌肉无力和昼夜行为变化。我们在不同的运动表型中观察到了适度但明确的缺陷，从而证实了这种转基因大鼠模型在治疗和药物研发方面的有效性。
