Department of Neurological Sciences, University of Nebraska Medical Center;
Department of Neurological Sciences, University of Nebraska Medical Center.
J Vis Exp. 2021 Jan 18(167). doi: 10.3791/62002.
Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. Gait abnormalities, including decreased arm swing, slower walking speed, and shorter steps are common in PD patients and appear early in the course of disease. Thus, the quantification of motor patterns in animal models of PD will be important for phenotypic characterization during disease course and upon therapeutic treatment. Most cases of PD are idiopathic; however, the identification of hereditary forms of PD uncovered gene mutations and variants, such as loss-of-function mutations in Pink1 and Parkin, two proteins involved in mitochondrial quality control that could be harnessed to create animal models. While mice are resistant to neurodegeneration upon loss of Pink1 and Parkin (single and combined deletion), in rats, Pink1 but not Parkin deficiency leads to nigral DA neuron loss and motor impairment. Here, we report the utility of FTIR imaging to uncover gait changes in freely walking young (2 months of age) male rats with combined loss of Pink1 and Parkin prior to the development of gross visually apparent motor abnormality as these rats age (observed at 4-6 months), characterized by hindlimb dragging as previously reported in Pink1 knockout (KO) rats.
帕金森病（PD）是一种进行性神经退行性疾病，由黑质致密部多巴胺能（DA）神经元丧失引起。步态异常，包括手臂摆动减少、行走速度较慢和步幅较短，在 PD 患者中很常见，并且在疾病早期就出现。因此，在 PD 动物模型中量化运动模式对于疾病过程中的表型特征描述以及治疗效果评估非常重要。大多数 PD 病例是特发性的；然而，遗传性 PD 病例的鉴定揭示了基因突变和变异，如 Pink1 和 Parkin 的功能丧失性突变，这两种蛋白参与线粒体质量控制，可以被用来创建动物模型。虽然在小鼠中，Pink1 和 Parkin（单敲除和双敲除）缺失并不导致神经退行性变，但在大鼠中，Pink1 而不是 Parkin 缺失会导致黑质 DA 神经元丧失和运动障碍。在这里，我们报告了傅里叶变换红外（FTIR）成像在 Pink1 和 Parkin 双敲除大鼠出现明显肉眼可见运动异常之前（在 4-6 月龄时观察到），揭示其自由行走时步态变化的应用，这些大鼠出现了运动障碍，表现为后肢拖拽，这与之前报道的 Pink1 敲除（KO）大鼠的情况相似。
