BASAL GANGLIA MOTOR CIRCUIT IN PARKINSON'S DISEASE

帕金森病中的基底神经节运动电路

• 批准号: 6112472
• 负责人: MAHLON R DELONG
• 金额: --
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112472
• 关键词: Macaca nemestrina; Parkinson's disease; abnormal involuntary movement; association cortex; basal ganglia; disease /disorder model; experimental brain lesion; lenticular nucleus; methylphenyltetrahydropyridine; motor cortex; neuropharmacology; nonhuman therapy evaluation; psychomotor function; sensorimotor system; stereotaxic techniques; thalamic nuclei; thalamocortical tract

The overall aim of the present study is to assess the role of pallidotomy in the treatment of experimental parkinsonism and to explore the mechanism, in the experimental MPTP monkey model of Parkinson's disease (PD), whereby pallidotomy ameliorates the signs of PD. The recent demonstration in the primate model of parkinsonism, of increased levels of neuronal activity in the subthalamic nucleus (STN) and globus pallidus pars intima (GPi) and the finding that inactivation of either the STN of GPi can reverse akinesia, tremor, and rigidity suggests that these abnormalities results from excessive (inhibitory) pallidal output. The finding that akinesia. Furthermore, the recent elucidation of specific subchannels in the sensorimotor portion of GPi related to different precentral motor areas (motor cortex [MC], supplementary motor area [SMA], premotor cortex [PMC]) raises the questions of whether different cardinal features of PD (akinesia, bradykinesia, rigidity, tremor and drug-induced dyskineasias) are related to dysfunction of these specific sub-circuits. As yet, however, there has been little work in the monkey models of PD to explore the effects of GPI lesions on experimental parkinsonism and drug-induced dyskinesias, and whether lesions in regions of GPi which interrupt specific subchannels will have a differential effect of parkinsonian motor signs and drug-induced dyskinesia. Consistent with the hypothesis that the pallido-thalamic "motor" circuits is responsible for the development of parkinsonian motor signs are earlier and recent reports that stereotactic lesions of the posteroventral (probable sensorimotor) portion of GPi in parkinsonian patients, can reverse the major motor abnormalities of PD as well as drug-induced dyskinesia. Thus, there is hope of improving motor function by surgical intervention for parkinsonian individuals who no longer derive benefit from medication or who cannot tolerate the dyskinesia and/or cognitive disturbances associated with drug therapy. Yet, much work remains to be done to determine which normalize activity in GPi while leaving the pallidothalamic projection and fibers passing through GPi intact, may be more effective. The studies in this proposal are directed at answering these questions. Specifically we will: 1) determine the optimal site of lesions in the pallidum for reversing parkinsonian motor signs and drug-induced dyskinesia, 2) determine whether specific subregions of GPi mediate specific parkinsonian signs (akinesia, bradykinesia, tremor and rigidity) and drug-induced dyskinesia, 3) determine whether bilateral lesions in GPi are more or less effective than GPi lesions in reversing parkinsonian motor sign and drug-induced dyskinesia.

本研究的总体目的是评估腹腔切开术的作用 在治疗实验帕金森氏症并探索 机制，在帕金森氏病的实验MPTP猴子模型中 （pd），骨膜切开术可以改善PD的迹象。 最近 在帕金森主义的灵长类动物模型中进行的演示，水平升高 丘脑下核（STN）和Globus Pallidus中神经元活性的 PARS Intima（GPI）和发现任何一种stn的发现 GPI可以逆转运动，震颤和僵化表明这些 异常是由于过度（抑制性）苍白球输出而导致的。 这 发现阿肯西尼亚。 此外，最近阐明了特定的 GPI的感觉运动部分中的亚通道与不同 前心电机区域（运动皮层[MC]，补充运动区域 [SMA]，前皮层[PMC]）提出了有关是否不同的问题 PD的基本特征（Akinesia，Bradykinesia，刚性，震颤和 药物诱导的心血管症）与这些特定的功能障碍有关 子电路。 但是，到目前为止，猴子几乎没有工作 PD的模型探索GPI病变对实验的影响 帕金森氏症和药物引起的运动障碍，以及地区的病变是否 中断特定亚渠道的GPI将具有差异 帕金森氏症运动标志和药物引起的运动障碍的影响。 与Pallido-Thalamic“ Motor”电路的假设一致 负责帕金森氏电动标志的发展是 早期和最近的报道，即立体定向病变 帕金森尼的GPI的后腹膜（可能的感觉运动）部分 患者可以扭转PD的主要运动异常 药物引起的运动障碍。 因此，有希望改善运动功能 通过对不再的帕金森病人的手术干预 从药物中获得好处或无法忍受运动障碍的人 和/或与药物治疗相关的认知障碍。 但是，很多 工作还有待确定GPI中的活动的正常 在离开pallidothalamic的投射和纤维穿过的同时 GPI完整，可能更有效。 该提议中的研究是 致力于回答这些问题。 具体我们将：1） 确定粒子中病变的最佳部位用于逆转 帕金森氏症和药物引起的运动障碍，2）确定 GPI的特定子区域是否介导了特定的帕金森氏症标志 （Akinesia，Bradykinesia，Tremor和刚性）和药物引起的 运动障碍，3）确定GPI中的双侧病变是更多还是 在扭转帕金森氏帕金森汽车标志和 药物引起的运动障碍。