CLINICAL AND PATHOLOGICAL AND BIOCHEMICAL STUDIES OF THE MECHANISM UNDERLYING DYSKINESIA AND FROZEN GAIT - PATHHOPHYSIOLOGICAL STUDY USING AUTOPSIED BRAINS OF PARKINSONIAN PATIENTS IN ADVANCED STAGES

运动障碍和冻结步态潜在机制的临床、病理学和生物化学研究 - 使用晚期帕金森病患者尸检大脑进行的病理生理学研究

基本信息

批准号：
10670602
负责人：
KONDO Tomoyoshi
金额：
$ 2.05万
依托单位：
WAKAYAMA MEDICAL COLLEGE (1999)Juntendo University (1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

With the long duration of Parkinson's disease, and problems encountered during its therapy, such as motor response fluctuations, dyskinesia, and levodopa-unresponsive symptoms, e.g., frozen gait, dementia develops. Although the pathophysiology of these symptoms has been described in reports of several animal experiments, the pathophysiology in parkinsonian patients has not been clarified. In this study, we analyzed biochemical markers in autopsied brains of patients with Parkinson's disease and correlated their activities or concentrations with their clinical symptoms, in order to investigate the pathophysiology of parkinsonism in humans. The biochemical markers examined in this study were tyrosine hydroxylase (TH) or dopamine (DA) as a marker of dopaminergic nerve terminals, norepinephrine (NE), GABA and glutamate (Glu) and neuropeptide (dynorphin). The brain regions in which the activity or concentrations of the above-mentioned substances were measured were the caudate nucleus and nucleus accumbens, putamen, substantia nigra, pallidum interna, pallidum externa, subthalamic nucleus. The obtained data were correlated with the clinical data of each patient ; that is, dyskinesia and wearing-off phenomenon were correlated with TH activity and levels of amino acids and dynorphin in the striatum, and frozen gait and dementia were correlated with DA and NE contents in the nucleus accumbens. There is no correlation between frozen gait, dementia and reduction in catecholamine content in the nucleus accumbens. Dyskinesia and the wearing-off phenomenon tended to correlate with a marked reduction in TH activity in the middle and caudal parts of the putamen. Results indicate that a marked reduction in dopaminaergic nerve terminals from the middle to caudal part of the putamen was a significant factor in the development of motor complications.

随着帕金森病的病程较长，以及治疗过程中遇到的问题，如运动反应波动、运动障碍和左旋多巴反应迟钝的症状，如步态僵硬，就会发展为痴呆。尽管一些动物实验报告中已经描述了这些症状的病理生理学，但帕金森病患者的病理生理学尚未阐明。在这项研究中，我们分析了帕金森病患者尸检大脑中的生化标记物，并将其活动或浓度与临床症状相关联，以研究人类帕金森病的病理生理学。本研究中检查的生化标志物是酪氨酸羟化酶（TH）或多巴胺（DA）作为多巴胺能神经末梢的标志物，去甲肾上腺素（NE），GABA和谷氨酸（Glu）以及神经肽（强啡肽）。测量上述物质的活性或浓度的脑区域是尾状核和伏核、壳核、黑质、内苍白球、外苍白球、底丘脑核。将获得的数据与每个患者的临床数据相关联；即运动障碍和减退现象与纹状体中TH活性以及氨基酸和强啡肽水平相关，冻结步态和痴呆与伏隔核中DA和NE含量相关。冻结步态、痴呆和伏隔核儿茶酚胺含量减少之间没有相关性。运动障碍和衰退现象往往与壳核中部和尾部 TH 活性的显着降低相关。结果表明，从壳核中部到尾部的多巴胺能神经末梢显着减少是运动并发症发生的一个重要因素。