Araki T, Tanji H, Kato H, Itoyama Y
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
J Neurol Sci. 1998 Oct 8;160(2):121-7. doi: 10.1016/s0022-510x(98)00248-2.
We investigated the sequential patterns of changes in dopamine uptake sites, D1 and D2 receptors in the brain of animals lesioned with 6-hydroxydopamine using quantitative receptor autoradiography. The rats were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks postlesion. Degeneration of the nigrostriatal pathway caused a significant loss of dopamine uptake sites in the ipsilateral striatum, substantia nigra (SN) and ventral tegmental area (VTA) in the lesioned animals. Dopamine D1 receptors were significantly increased in the ventromedial part of striatum of the ipsilateral side from 2 to 4 weeks postlesion. In the ipsilateral SN, a transient increase in dopamine D1 receptors was observed only 1 week after lesioning. However, the frontal cortex, parietal cortex and dorsolateral part of the striatum showed no significant change in dopamine D1 receptors throughout the experiments. On the other hand, dopamine D2 receptors were decreased increased in the ipsilateral SN and VTA from 1 week to 8 weeks postlesion. In the ipsilateral striatum, dopamine D2 receptors were increased in the dorsolateral part from 2 weeks to 8 weeks and in the ventromedial part from 2 weeks to 4 weeks. However, the frontal cortex and parietal cortex showed no significant change in dopamine D2 receptors during postlesion. In the contralateral side, most of regions examined showed no significant change in dopamine uptake sites, dopamine D1 receptors and dopamine D2 receptors during postlesion except for a transient change in a few regions. These results demonstrate that 6-hydroxydopamine can cause a severe functional damage in dopamine uptake sites in the striatum, SN and VTA. Our findings also suggest that the up-regulation in dopamine D2 receptors is more pronounced than that in dopamine D1 receptors in the brain after 6-hydroxydopamine treatment. Furthermore, our results support the existence of dopamine D2 receptors on the neurons of SN and VTA. Thus, our findings provide insights into the pathogenesis of Parkinson's disease.
我们使用定量受体放射自显影技术，研究了用6-羟基多巴胺损伤的动物大脑中多巴胺摄取位点、D1和D2受体的变化顺序模式。大鼠单侧损毁内侧前脑束，并在损伤后1、2、4和8周对大脑进行分析。黑质纹状体通路的退化导致损伤动物同侧纹状体、黑质（SN）和腹侧被盖区（VTA）的多巴胺摄取位点显著丧失。损伤后2至4周，同侧纹状体腹内侧部分的多巴胺D1受体显著增加。在同侧SN中，仅在损伤后1周观察到多巴胺D1受体短暂增加。然而，在整个实验过程中，额叶皮质、顶叶皮质和纹状体背外侧部分的多巴胺D1受体没有显著变化。另一方面，损伤后1周龄至8周龄，同侧SN和VTA中的多巴胺D2受体减少增加。在同侧纹状体中，背外侧部分的多巴胺D2受体从2周龄至8周龄增加，腹内侧部分从2周龄至4周龄增加。然而，额叶皮质和顶叶皮质在损伤后多巴胺D2受体没有显著变化。在对侧，除少数区域有短暂变化外，大多数检查区域在损伤后多巴胺摄取位点、多巴胺D1受体和多巴胺D2受体没有显著变化。这些结果表明，6-羟基多巴胺可导致纹状体、SN和VTA中多巴胺摄取位点的严重功能损伤。我们的研究结果还表明，6-羟基多巴胺治疗后，大脑中多巴胺D2受体的上调比多巴胺D1受体更明显。此外，我们的结果支持SN和VTA神经元上存在多巴胺D2受体。因此，我们的研究结果为帕金森病的发病机制提供了见解。
