REGULATION OF MOTOR FUNCTION IN PARKINSON'S DISEASE

帕金森病运动功能的调节

• 批准号: 7562574
• 负责人: STELLA PAPPA
• 金额: $ 3.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562574
• 关键词: Basal Ganglia; Behavior; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Dopamine; Dose; Dyskinetic syndrome; Fire - disasters; Frequencies; Funding; Glutamates; Goals; Grant; Injection of therapeutic agent; Institution; Levodopa; Mediating; Molecular Conformation; Motor; Neurons; Output; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Pattern; Rate; Regulation; Research; Research Personnel; Resources; Source; Symptoms; United States National Institutes of Health; disability; drug testing; ion channel blocker; neurotransmission; novel; novel therapeutics; research study; tool

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. The objective of this project is to elucidate the pathophysiologic mechanisms of abnormal behaviors in Parkinson's disease with the goal of developing new therapeutic tools. Thus, this study aims: 1-to characterize basal ganglia functional alterations, 2-to determine the glutamatergic regulation associated with an altered neuronal function, and 3-to explore new therapeutic approaches by interacting with the glutamatergic neurotransmission. This project has made great progress during the last period. Our previous findings suggested that dyskinesias are produced by mechanisms that overturn dopamine action on striatal neurons. However, the specific relationship of those rate changes to the occurrence of dyskinesias remained uncertain. This year, we recorded the activity of striatal neurons in experiments of lower doses of levodopa. Firing rates of striatal neurons did not show inversion of changes during the 'on' state when dyskinesias were not present. These results proved our novel findings of inversion of dopamine-induced rate changes in striatal neurons that is mechanistically associated with dyskinesias. Regarding the pattern of neuronal activity, we found that reversal of parkinsonian disability was characterized by a reduction of bursting and changes in burst conformation. Most 'bursty' neurons also increased their frequency during the transition to reversal of parkinsonism implying that dopamine mediates excitatory mechanisms in these neurons, thereby involving the direct output pathway. From results of pattern analysis so far, we can conclude that parkinsonian motor symptoms are associated with burst discharges in a subpopulation of striatal neurons. Drug tests performed this year indicate that ion channel blockers appear to be highly effective for initial local injections.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目的是阐明帕金森病异常行为的病理生理机制，以开发新的治疗工具为目标。 因此，本研究旨在：1-表征基底神经节功能改变，2-确定与改变的神经元功能相关的多巴胺能调节，和3-通过与多巴胺能神经传递相互作用探索新的治疗方法。 这个项目在过去的一段时间里取得了很大的进展。我们先前的研究结果表明，运动障碍是由推翻多巴胺对纹状体神经元作用的机制产生的。 然而，这些速率变化与运动障碍发生的具体关系仍不确定。 今年，我们在低剂量左旋多巴的实验中记录了纹状体神经元的活动。纹状体神经元的放电率并没有表现出反转的变化，在'上'的状态时，运动障碍不存在。这些结果证明了我们的新发现，多巴胺诱导的纹状体神经元的速率变化，这是与运动障碍的机制相关的反转。关于神经元活动的模式，我们发现，帕金森氏症残疾的逆转的特点是减少爆裂和爆裂构象的变化。 大多数'突发'神经元也增加了他们的频率在过渡到帕金森氏症的逆转，这意味着多巴胺介导的兴奋机制，在这些神经元，从而涉及直接输出通路。从迄今为止的模式分析结果，我们可以得出结论，帕金森病运动症状与纹状体神经元亚群的爆发性放电有关。今年进行的药物试验表明，离子通道阻滞剂似乎对初始局部注射非常有效。