Temporal changes of dopaminergic and glutamatergic receptors in 6-hydroxydopamine-treated rat brain
Temporal changes of dopaminergic and glutamatergic receptors in 6-hydroxydopamine-treated rat brain
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DOI：
10.1016/s0924-977x(00)00094-8
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发表时间：
2000-09-01
影响因子：
5.6
通讯作者：
Itoyama, Y
中科院分区：
文献类型：
--
作者：
Araki, T;Tanji, H;Itoyama, Y
定量受体放射自显影用于检查 6-羟基多巴胺损伤的大鼠大脑中多巴胺能和谷氨酸能受体变化的连续模式。对动物的内侧前脑束进行单侧损伤，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同侧纹状体中多巴胺 D-2 受体在病变后 1 至 8 周显着增加。在同侧黑质 (SN) 中，在病变后 1 至 8 周内还观察到多巴胺 D-2 受体显着减少。另一方面，病变后 3 至 4 周，同侧腹内侧纹状体中的多巴胺 D-1 受体增加。在同侧 SN 中，仅在损伤后 1 周就观察到多巴胺 D-1 受体短暂增加。然而，除了少数区域短暂变化外，同侧和对侧的其他区域在病变后多巴胺D-1和D-2受体没有显着变化。在损伤后研究的所有大脑区域中，N-甲基-D-天冬氨酸 (NMDA) 受体均未显示显着变化。相反，在损伤后两周，仅在同侧的额叶皮层和腹内侧纹状体中观察到兴奋性氨基酸转运位点的短暂增加。然而，损伤后同侧和对侧任何脑区的甘氨酸受体均显示出显着变化。对侧脑区甘氨酸受体的变化较同侧更为明显。此外，损伤后1至8周，同侧纹状体的多巴胺摄取位点显示出严重损伤。相反，在对侧，在病变后纹状体中多巴胺摄取位点没有发现显着变化。这些结果表明，在内侧前脑束中单侧注射6-羟基多巴胺可以引起纹状体中多巴胺D-1和D-2受体的显着增加。 6-羟基多巴胺治疗后，纹状体中多巴胺 D-2 受体的增加比多巴胺 D-1 受体的增加更明显。相比之下，多巴胺摄取位点在病变后纹状体中显示出严重损伤。此外，我们的结果支持 SN 神经元上存在多巴胺 D-2 受体，但不支持多巴胺 D-1 受体。对于谷氨酸能受体系统，本研究表明甘氨酸受体的变化可能比NMDA受体和兴奋性氨基酸转运位点更容易受到黑质纹状体途径变性的影响。因此，我们的研究结果对帕金森病中发生的黑质纹状体通路变性的关系很感兴趣 (C) 2000 Elsevier Science B.V. 保留所有权利。
Quantitative receptor autoradiography was used to examine the sequential patterns of changes in dopaminergic and glutamatergic receptors in the brain of rats lesioned with 6-hydroxydopamine. The animals were unilaterally lesioned in the medial forebrain bundle and the brains were analyzed at 1, 2, 4 and 8 weeks of postlesion. Degeneration of the nigrostriatal pathway caused a significant increase in dopamine D-2 receptors in the ipsilateral striatum from 1 to 8 weeks of postlesion. In the ipsilateral substantia nigra (SN), a significant decrease in dopamine D-2 receptors was also observed from 1 to 8 weeks of postlesion. On the other hand, dopamine D-1, receptors were increased in the ipsilateral ventromedial striatum from 3 to 4 weeks of postlesion. In the ipsilateral SN, a transient increase in dopamine D-1 receptors was observed only 1 week after lesioning. However, other regions in both ipsilateral and contralateral sides showed no significant change in dopamine D-1, and D-2, receptors during postlesion except for a transient change in a few regions. N-Methyl-D-aspartate (NMDA) receptors showed no significant changes in all brain regions studied during the postlesion. In contrast, a transient increase in excitatory amino acid transport sites was observed only in the frontal cortex and ventromedial striatum of the ipsilateral side at 2 weeks of postlesion. However, glycine receptors showed a significant change in any brain areas of both ipsilateral and contralateral sides after lesioning. The change in the brain areas of contralateral side was more pronounced than that of ipsilateral side for glycine receptors. In addition, dopamine uptake sites showed a severe damage in the ipsilateral striatum from 1 to 8 weeks after lesioning. In the contralateral side, in contrast, no significant change in dopamine uptake sites was found in the striatum during the postlesion. These results indicate that unilateral injection of 6-hydroxydopamine in the medial forebrain bundle can cause a significant increase in dopamine D-1 and D-2 receptors in the striatum. The increase in dopamine D-2, receptors was more pronounced than that in dopamine D-1 receptors in the striatum after 6-hydroxydopamine treatment. In contrast, dopamine uptake sites showed a severe damage in the striatum during the postlesion, Furthermore, our results support the existence of dopamine D-2 receptors on the neurons of SN, but not dopamine D-1 receptors. For glutamatergic receptor system, the present study suggests that the changes in glycine receptors may be more susceptible to degeneration of nigrostriatal pathway than NMDA receptors and excitatory amino acid transport sites. Thus, our findings are of interest in relation of degeneration of the nigrostriatal pathway that occurs in Parkinson's disease (C) 2000 Elsevier Science B.V. All rights reserved.