REGULATION OF MOTOR FUNCTION IN PARKINSON'S DISEASE

帕金森病运动功能的调节

• 批准号: 7349230
• 负责人: STELLA PAPPA
• 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/7349230
• 关键词: Parkinson' s disease; autoradiography; basal ganglia; behavior; conditioning; denervation; dopamine; glutamates; lenticular nucleus; levodopa; neural transmission; neurons; person with disability

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. Motor disturbances of Parkinson?s disease are caused by a series of functional alterations in basal ganglia that derive from dopamine denervation. The mechanisms underlying those functional alterations are not completely understood. Moreover, long-term levodopa therapy is usually associated with disabling motor complications of unclear pathophysiology. The objective of this project is to elucidate the pathophysiologic mechanisms of abnormal behaviors in Parkinson?s disease in view of developing new therapeutic tools. Thus, this study aims: to localize functional alterations in specific basal ganglia circuits; to determine the glutamate regulation associated with an altered neuronal function; to explore new therapeutic approaches by interacting with the glutamatergic neurotransmission in a region-specific manner. This project has made great progress during the last period, and we are completing a big part of specific aim 1. The neuronal activity of striatum has been studied in various motor conditions. We have generated abundant data to fully characterize patterns of activity that specifically correlate to motor states in parkinsonism. Recordings in other regions have started, i.e. globus pallidus, both segments. We are also working on the second specific aim by initiating autoradiography studies. Firing rates change with the reversal of parkinsonism following two directions, increase and decrease, and this is congruent with the dual action of levodopa on striatal neurons. The appearance of dyskinesias is associated with inversion in the direction of rate changes. This pattern of activity indicates that dyskinesias are produced by different mechanisms than those operating the reversal of parkinsonism. These changes are observed in striatal neurons with bursty and non-bursty activity. These cells also change patterns of activity in relation to motor states. The latest analyses of striatal activity data indicate that bursts are linked to akinesia and other features of parkinsonism, while other patterns such as pausing and irregularity correlate with dyskinesias.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。帕金森-S病的运动障碍是由多巴胺失神经引起的一系列基底节功能改变引起的。这些功能改变背后的机制尚不完全清楚。此外，长期的左旋多巴治疗通常与病理生理学不明的运动障碍相关。本课题旨在阐明帕金森-S病异常行为的病理生理机制，以期开发新的治疗手段。因此，本研究的目的是：定位特定基底节回路的功能改变；确定与神经元功能改变相关的谷氨酸调节；通过与谷氨酸能神经递质以区域特异性的方式相互作用来探索新的治疗方法。该项目在过去的一段时间里取得了很大的进展，我们正在完成特定目标的很大一部分1。研究了不同运动条件下纹状体神经元的活动。我们已经产生了大量的数据来充分描述与帕金森症运动状态具体相关的活动模式。在其他地区的录制已经开始，即苍白球，这两个部分。我们还在通过启动放射自显影研究来实现第二个具体目标。放电频率随着帕金森病的逆转而改变，遵循增加和减少两个方向，这与左旋多巴对纹状体神经元的双重作用是一致的。运动障碍的出现与心率变化方向的倒置有关。这种活动模式表明，运动障碍是由不同的机制产生的，而不是那些逆转帕金森症的机制。在突发性和非突发性活动的纹状体神经元中可以观察到这些变化。这些细胞还会改变与运动状态相关的活动模式。对纹状体活动数据的最新分析表明，猝发与运动迟缓和帕金森症的其他特征有关，而其他模式，如停顿和不规则，则与运动障碍有关。