Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Brain Res. 2010 Jan 8;1306:176-83. doi: 10.1016/j.brainres.2009.09.103. Epub 2009 Oct 3.
Parkinson's disease (PD) is caused by selective degeneration of the nigral dopaminergic (DArgic) neurons and is accompanied by motor dysfunctions such as tremor, akinesia, and rigidity. Changes in the degree of motor deficit can be utilized as a noninvasive way of assessing alterations in the number of DArgic neurons and/or the amount of DA in animal models of PD, such as mice systemically administrated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, in order to develop sensitive methods to detect DA-associated motor deficits, we designed a new test called vertical grid test and modified the existing horizontal grid test. After acute MPTP treatment, decreases in the levels of striatal DA (17.4% of control), dihydroxyphenylacetic acid (33.3%), and homovanillic acid (40.5%) were observed. On the modified horizontal grid test, the MPTP-administered mice exhibited average forelimb step distance that was lower than control (82.58%) and correlated with the striatal DA levels. On the vertical grid test, the MPTP-treated mice took dramatically longer total time to climb down (220.94%) and time to make the turn (339.29%) compared to control, and this correlated well with the degree of striatal DA depletion. In comparison, the gait test produced only a small, albeit statistically significant, reduction in the mean stride length (94.55% of control). These results show that the vertical grid test can provide a sensitive measure of motor deficit in mice following administration of MPTP.
帕金森病（PD）是由黑质多巴胺能（DArgic）神经元选择性退化引起的，伴有震颤、运动迟缓、僵硬等运动功能障碍。运动缺陷程度的变化可作为评估 PD 动物模型（如系统性给予 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的小鼠）中 DArgic 神经元数量和/或 DA 含量变化的非侵入性方法。在这项研究中，为了开发检测与 DA 相关的运动缺陷的敏感方法，我们设计了一种称为垂直网格测试的新测试，并改进了现有的水平网格测试。急性 MPTP 处理后，纹状体 DA（对照的 17.4%）、二羟苯乙酸（33.3%）和高香草酸（40.5%）水平降低。在改良的水平网格测试中，MPTP 给药的小鼠表现出低于对照（82.58%）的平均前肢步距，并且与纹状体 DA 水平相关。在垂直网格测试中，与对照相比，MPTP 处理的小鼠下降的总时间（220.94%）和转弯时间（339.29%）明显更长，并且与纹状体 DA 耗竭程度相关良好。相比之下，步态测试仅使平均步幅长度略有降低（对照的 94.55%），但具有统计学意义。这些结果表明，垂直网格测试可以为 MPTP 给药后小鼠的运动缺陷提供敏感的测量。
