Department of Anatomy and Neurobiology, Northeastern Ohio Universities College of Medicine, Rootstown, OH 44272-0095, USA.
Neurosci Lett. 2010 May 31;476(2):66-9. doi: 10.1016/j.neulet.2010.04.004. Epub 2010 Apr 9.
In this report we compared three different parameters of nigrostriatal dopaminergic (NSDA) function - locomotor activity, striatal dopamine (DA) levels and 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratios between heterozygous mutant dopamine transporter mice (+/- DAT) and their wild type controls (+/+ DAT) at three different age range periods: 4-10, 11-17 and 18-24 months of age. Locomotor activity of the +/- DAT mice failed to differ over the three age periods sampled. In +/+ DAT mice a significant decrease in locomotor activity was obtained at the 18-24-month old period compared with scores at the two earlier age periods. In addition, locomotor scores of +/+ DAT mice at 18-24 months of age were significantly decreased as compared with scores of the +/- DAT mice at this age. Striatal DA concentrations of +/- DAT mice also failed to differ over the three age periods sampled, while that of +/+ DAT mice showed significant decreases in striatal DA at 11-17 and 18-24 months of age as compared to their 4-10-month old cohorts. Striatal DOPAC/DA ratios were significantly increased in both +/+ and +/- DAT mice at the 11-17 and 18-24 month age periods as compared with their respective 4-10-month old groups. Striatal DOPAC/DA ratios of +/- DAT mice were significantly greater than that of the +/+ DAT mice at 18-24 months of age. These findings reveal the significance of interactions between a mutation of the dopamine transporter and aging upon NSDA function and the importance of isolating such variables when using knock-out models.
在本报告中，我们比较了三种不同的黑质纹状体多巴胺能（NSDA）功能参数——运动活性、纹状体多巴胺（DA）水平和 3,4-二羟基苯乙酸（DOPAC）/DA 比值，在三个不同的年龄范围期间：4-10 个月、11-17 个月和 18-24 个月，对杂合突变多巴胺转运体小鼠（ +/- DAT）与其野生型对照（+ / + DAT）进行了比较。 +/- DAT 小鼠的运动活性在三个采样年龄阶段没有差异。在 + / + DAT 小鼠中，与前两个年龄阶段相比，在 18-24 个月大的时期，运动活性显著下降。此外，+ / + DAT 小鼠在 18-24 个月大时的运动评分与该年龄 +/- DAT 小鼠的评分相比显著降低。 +/- DAT 小鼠的纹状体 DA 浓度在三个采样年龄阶段也没有差异，而 + / + DAT 小鼠的纹状体 DA 浓度在 11-17 个月和 18-24 个月时与 4-10 个月大的群体相比显著降低。与各自的 4-10 个月大的组相比，+ / + 和 +/- DAT 小鼠在 11-17 个月和 18-24 个月大时纹状体 DOPAC/DA 比值均显著增加。在 18-24 个月大时， +/- DAT 小鼠的纹状体 DOPAC/DA 比值明显大于 + / + DAT 小鼠。这些发现揭示了多巴胺转运体突变与衰老对 NSDA 功能的相互作用的重要性，以及在使用敲除模型时分离这些变量的重要性。
