REGULATION OF MOTOR FUNCTION IN PARKINSON'S DISEASE

帕金森病运动功能的调节

• 批准号: 8357414
• 负责人: Stella M Papa
• 金额: $ 4.12万
• 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/8357414
• 关键词: Cannabinoids; Chronic; Corpus striatum structure; Dopamine; Dopamine Receptor; Dopaminergic Agents; Evolution; Excitatory Amino Acid Antagonists; Functional disorder; Funding; Globus Pallidus; Glutamates; Goals; Grant; Hyperactive behavior; Infusion procedures; Injection of therapeutic agent; Levodopa; Mediating; Monkeys; Motor; National Center for Research Resources; Neurons; Neurotransmitters; Output; Parkinson Disease; Parkinsonian Disorders; Pharmaceutical Preparations; Play; Primates; Principal Investigator; Regulation; Research; Research Infrastructure; Resources; Role; Source; Staging; Symptoms; System; United States National Institutes of Health; base; cost; putamen; response; transmission process

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. This project evaluates the pathophysiology of abnormal motor symptoms developed in the evolution of Parkinson's disease (PD). Dopamine replacement has beneficial effects in the early stages, but long-term therapy often fails to completely restore normal mobility, and may even produce additional motor abnormalities. Altered dopamine responses have been related to changes in dopamine receptor-mediated mechanisms regulating the activity of striatal neurons. However, changes in other neurotransmitter systems may also play a role. Based on our previous studies in this project, we focus our continuation studies on the role of striatal glutamatergic transmission in the pathophysiology of abnormal responses to levodopa. The goal of these studies is to identify pharmacologic targets that could serve to develop new treatments for the long-term therapy of PD. The project comprises four aims: (1) To study the relationship between glutamatergic hyperactivity and altered discharges of striatal medium spiny neurons (MSNs) in parkinsonian monkeys. Electrophysiologic recordings of MSNs are combined with striatal injections of specific glutamate receptor antagonists. (2) To examine whether increased glutamate release is involved in the altered MSN discharges. We will reduce glutamatergic levels with cannabinoid CB1-acting drugs infused into the putamen of parkinsonian monkeys to study MSN firing changes and levodopa motor responses. (3) To study the changes in indirect striatal outputs that develop in chronic PD and are associated with abnormal responses to dopaminergic drugs. We will use glutamate antagonists in putaminal infusions and record the neuronal activity of the external segment of the globus pallidus in normal and parkinsonian monkeys.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 该项目评估了帕金森氏病（PD）发展中异常运动症状的病理生理。多巴胺替代在早期阶段具有有益的作用，但是长期治疗通常无法完全恢复正常的活动能力，甚至可能产生额外的运动异常。多巴胺反应改变与调节纹状体神经元活性的多巴胺受体介导的机制的变化有关。 但是，其他神经递质系统的变化也可能起作用。基于我们先前在该项目中的研究，我们将继续研究集中在纹状体谷氨酸能传播在对左旋多巴异常反应的病理生理学中的作用。这些研究的目的是确定可以为PD长期治疗开发新疗法的药理学靶标。该项目包括四个目的：（1）研究帕金森尼猴子中谷氨酸能多动症与纹状体培养基神经元（MSN）的放电之间的关系。 MSN的电生理记录与特定谷氨酸受体拮抗剂的纹状体注射结合。 （2）检查改变的MSN放电是否涉及谷氨酸释放增加。我们将使用注入帕克森尼猴子的大麻素CB1作用药物来降低谷氨酸能水平，以研究MSN发射变化和左旋多巴运动反应。 （3）研究在慢性PD中发展的间接纹状体输出的变化，并与对多巴胺能药物的异常反应有关。我们将在phut脉输注中使用谷氨酸拮抗剂，并记录正常和帕金森尼猴子中球pallus pallidus外部段的神经元活性。