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Behavioral tests predicting striatal dopamine level in a rat hemi-Parkinson's disease model.
Neurochemistry international ( IF 4.4 ) Pub Date : 2018-11-09 , DOI: 10.1016/j.neuint.2018.11.005 Kazuya Miyanishi 1 , Mohammed E Choudhury 1 , Minori Watanabe 1 , Madoka Kubo 2 , Masahiro Nomoto 2 , Hajime Yano 1 , Junya Tanaka 1
Neurochemistry international ( IF 4.4 ) Pub Date : 2018-11-09 , DOI: 10.1016/j.neuint.2018.11.005 Kazuya Miyanishi 1 , Mohammed E Choudhury 1 , Minori Watanabe 1 , Madoka Kubo 2 , Masahiro Nomoto 2 , Hajime Yano 1 , Junya Tanaka 1
Affiliation
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Parkinson's disease (PD) is a frequent neurodegenerative disease causing bradykinesia, tremor, muscle rigidity and postural instability. Although its main pathology is progressive dopaminergic (DArgic) neuron loss in the substantia nigra, motor deficits are thought not to become apparent until most DArgic neurons are lost, probably due to compensatory mechanisms that overcome the decline of DA level in the striatum. Even in animal PD models, it is difficult to detect motor deficits when most DArgic neurons are functional. In this study, we performed various behavioral tests (apomorphine-induced rotation, cylinder, forepaw adjustment steps (FAS), beam walking, rota-rod, and open-field), using 6-hydroxydopamine (OHDA) and lipopolysaccharide (LPS)-induced hemi-PD model rats with various striatal DA levels, to find the best way to predict the DA level from earlier disease stages. Different from the 6-OHDA-induced model, reduction in the striatal DA levels in the LPS-model was less significant. Among the behavioral tests, data from cylinder and FAS tests, which evaluate forelimb movements, best correlated with decline of the DA level. They also correlated well with decreased body weight gain. The beam and apomorphine tests showed less significant correlation than the cylinder and FAS tests. Open-field and rota-rod tests were not useful. Expressional levels of mRNA encoding tyrosine hydroxylase (TH), a marker of DArgic neurons, correlated well with the DA level. Metabotropic glutamate receptor 4 mRNA expression correlated with the striatal DA level and may be related to compensatory mechanisms. These results suggest that motor impairments of PD should be evaluated by forelimb movements, or hands and forearms in clinical settings, rather than movement of the body or large joints. The combination of cylinder and FAS tests may be the best to evaluate the rat PD models, in which many DArgic neurons survive.
中文翻译：
行为测试预测大鼠半帕金森氏病模型中的纹状体多巴胺水平。
帕金森氏病（PD）是一种常见的神经退行性疾病，会导致运动迟缓，震颤，肌肉僵硬和姿势不稳。尽管其主要病理是黑质中进行性多巴胺能（DArgic）神经元的丧失，但据认为直到大多数DArgic神经元丧失，运动功能障碍才变得明显，这可能是由于克服了纹状体DA水平下降的补偿机制所致。即使在动物PD模型中，当大多数DArgic神经元都起作用时，也很难检测到运动功能障碍。在这项研究中，我们使用6-羟基多巴胺（OHDA）和脂多糖（LPS）-诱导的具有不同纹状体DA水平的半PD模型大鼠，寻找从疾病早期阶段预测DA水平的最佳方法。与6-OHDA诱导的模型不同，LPS模型中纹状体DA水平的降低不那么显着。在行为测试中，来自圆柱体和FAS测试的数据（评估前肢运动）与DA水平的下降最相关。他们还与体重增加减少密切相关。束和阿扑吗啡试验显示的相关性不如圆柱体和FAS试验。开场和旋转杆测试没有用。编码酪氨酸羟化酶（TH）（DArgic神经元的标志物）的mRNA的表达水平与DA水平相关性很好。代谢型谷氨酸受体4 mRNA的表达与纹状体DA水平相关，可能与代偿机制有关。这些结果表明，PD的运动障碍应通过前肢运动或临床环境中的手和前臂运动来评估，而不是通过身体或大关节的运动来评估。圆柱和FAS测试的组合可能是评估大鼠PD模型的最佳方法，其中许多DArgic神经元都可以存活。
更新日期：2018-11-09
中文翻译：
行为测试预测大鼠半帕金森氏病模型中的纹状体多巴胺水平。
帕金森氏病（PD）是一种常见的神经退行性疾病，会导致运动迟缓，震颤，肌肉僵硬和姿势不稳。尽管其主要病理是黑质中进行性多巴胺能（DArgic）神经元的丧失，但据认为直到大多数DArgic神经元丧失，运动功能障碍才变得明显，这可能是由于克服了纹状体DA水平下降的补偿机制所致。即使在动物PD模型中，当大多数DArgic神经元都起作用时，也很难检测到运动功能障碍。在这项研究中，我们使用6-羟基多巴胺（OHDA）和脂多糖（LPS）-诱导的具有不同纹状体DA水平的半PD模型大鼠，寻找从疾病早期阶段预测DA水平的最佳方法。与6-OHDA诱导的模型不同，LPS模型中纹状体DA水平的降低不那么显着。在行为测试中，来自圆柱体和FAS测试的数据（评估前肢运动）与DA水平的下降最相关。他们还与体重增加减少密切相关。束和阿扑吗啡试验显示的相关性不如圆柱体和FAS试验。开场和旋转杆测试没有用。编码酪氨酸羟化酶（TH）（DArgic神经元的标志物）的mRNA的表达水平与DA水平相关性很好。代谢型谷氨酸受体4 mRNA的表达与纹状体DA水平相关，可能与代偿机制有关。这些结果表明，PD的运动障碍应通过前肢运动或临床环境中的手和前臂运动来评估，而不是通过身体或大关节的运动来评估。圆柱和FAS测试的组合可能是评估大鼠PD模型的最佳方法，其中许多DArgic神经元都可以存活。
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