GABA-B RECEPTORS AND PARKINSON'S DISEASE

GABA-B 受体与帕金森病

• 批准号: 7349151
• 负责人: Yoland Smith
• 金额: $ 4.01万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-09 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349151
• 关键词: GABA receptor; Macaca mulatta; basal ganglia; lenticular nucleus; microdialysis; neurons; play; receptor; role; GABA receptor; Macaca mulatta; basal ganglia; lenticular nucleus; microdialysis; neurons; play; receptor; role

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project aims at studying the localization, functions and potential antiparkinsonian benefits of GABAB receptor modulation in monkeys. To achieve these goals we use various immunocytochemical and functional approaches that include high resolution immunogold procedures at the electron microscopic level, microdialysis techniques, in vivo single unit recording in rhesus monkey basal ganglia and behavioral testing in parkinsonian monkeys. Over the past year, we demonstrated that GABA-B receptors are widely expressed pre- and post-synaptically in the monkey globus palidus and subthalamic nucleus. Furthermore, we have also shown that local intracereberal injection of both GABA-A and GABA-B receptor agonists has strong inhibitory effects in the monkey globus pallidus. In addition, we provided clear evidence that increased GABA spillover in the globus pallidus, through blockade of GABA transporters play an important role in mediating inhibitory influences towards pallidal neurons in monkeys. Together, these functional and anatomical data emphasize the importance of extrasynaptic GABA receptors in controlling neuronal activity in the basal ganglia. Ongoing experiments are in progress to assess the role of extrasynaptic GABA receptors in parkinsonians.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。该项目旨在研究猴子中GABAB受体调制的本地化，功能和潜在的反帕金森氏益处。为了实现这些目标，我们使用各种免疫细胞化学和功能方法，包括电子显微镜水平上的高分辨率免疫原过程，微透析技术，在鼠尾草猴子基底神经节中的体内单位记录和帕金森猴中的行为测试。在过去的一年中，我们证明了GABA-B受体在猴子球和丘脑下核中被广泛表达。此外，我们还表明，GABA-A和GABA-B受体激动剂的局部骨内注射在猴子帕利德斯中具有强大的抑制作用。此外，我们提供了明确的证据表明，通过封锁GABA转运蛋白在介导对猴子的苍白神经元的抑制作用中，通过阻断Gabus Pallidus的GABA溢出量增加了重要作用。这些功能和解剖学数据共同强调了外部GABA受体在控制基底神经节神经元活性中的重要性。正在进行的实验正在进行中，以评估帕金森氏症中肌周外GABA受体的作用。