EXTRASTRIATAL FUNCTIONS OF DOPAMINE

多巴胺的纹外功能

• 批准号: 8357574
• 负责人: Thomas N Wichmann
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357574
• 关键词: Animals; Antiparkinson Agents; Corpus striatum structure; Development; Dopamine; Dopamine Agonists; Dopamine Receptor; Electron Microscopy; Fiber; Funding; Grant; Ligands; Macaca mulatta; Monkeys; National Center for Research Resources; Neurons; Parkinsonian Disorders; Pathologic; Pattern; Play; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Rodent; Role; Source; Structure of subthalamic nucleus; Substantia nigra structure; United States National Institutes of Health; cost; density; dopaminergic neuron; nerve supply; pars compacta; postsynaptic; presynaptic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Parkinsonism arises from degeneration of dopaminergic neurons in the substantia nigra pars compacta and resulting abnormal neuronal activity patterns in the external and internal pallidal segments and in the subthalamic nucleus (STN). While the development of these pathologic activity patterns has been explained as the result of striatal dopamine loss, due to degeneration of the nigrostriatal tract, recent studies demonstrate that extrastriatal dopamine loss may also play a significant role. Our studies are examining this issue, focusing on the dopamine supply to the primate STN. We have started to analyze the extent of the dopaminergic innervation and characterize the ultrastructural localization of dopamine receptors within STN of normal and MPTP-treated parkinsonian monkeys in 11 Rhesus monkeys. We found that MPTP-treatment reduces the density of dopaminergic fibers in the STN. Ongoing studies characterize the anatomical distribution and density of dopamine receptors in the STN, using electron microscopy. We have also carried out studies of the effects of dopamine receptor ligands on the electrophysiologic STN activity. Studies in one normal animal were completed. This animals is currently being studied in the MPTP-treated state. Studies in rodents have suggested that activation of pre- and postsynaptic dopamine receptors in the STN increases neuronal firing and reduces bursting. Both actions would be considered antiparkinsonian, suggesting that dopamine receptor agonists may exert some of their beneficial antiparkinsonian effects in STN.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 帕金森综合征是由黑质丘脑部多巴胺能神经元的变性引起的，并导致苍白球外部和内部节段以及丘脑底核（subthalamic nucleus，丘脑底核）中的异常神经元活动模式。 虽然这些病理活动模式的发展已被解释为纹状体多巴胺丢失的结果，由于黑质纹状体束的变性，最近的研究表明，纹状体外多巴胺丢失也可能发挥重要作用。 我们的研究正在研究这个问题，重点是灵长类动物大脑的多巴胺供应。 我们已经开始分析多巴胺能神经支配的程度和特点的多巴胺受体的超微结构定位正常和MPTP治疗帕金森病猴在11只恒河猴脑内。 我们发现，MPTP治疗降低多巴胺能纤维的密度在延髓。 目前正在进行的研究特征的解剖分布和密度的多巴胺受体在小脑，使用电子显微镜。我们还进行了多巴胺受体配体对电生理活动的影响的研究。 在一只正常动物中完成了研究。 该动物目前正在MPTP给药状态下进行研究。 对啮齿类动物的研究表明，突触前和突触后多巴胺受体的激活增加了神经元的放电，减少了爆发。 这两种作用都被认为是抗帕金森病的，表明多巴胺受体激动剂可能在帕金森病中发挥一些有益的抗帕金森病作用。