BENZODIAZEPINE RECEPTORS IN NEURODEGENERATIVE DISEASES

这是对继续支持研究的请求 γ-氨基丁酸(GABA)-A/苯二氮杂二氮的浓度 中枢神经系统中的神经递质受体 进行性核上性神经退行性疾病 麻痹(PSP)，并将研究结果与认知和 这种疾病中的运动障碍。有证据表明 这些受体的变化可能在 这种疾病的病理生理学。 在PSP中，认知和运动障碍被认为是 皮质下神经病变所致 结构，但正电子发射断层扫描(PET)研究 与[18F]氟代脱氧葡萄糖(FDG)显示广泛 中枢神经系统(CNS)的低代谢， 包括大脑皮层。这增加了一种可能性 认知障碍是由大脑皮质引起的 而不是皮质下的病理学。开发一种新的 配体[11C]氟马西尼(FMZ)，用于研究γ-氨基丁酸 酸(GABA)-A/苯二氮(BDZ)神经递质 受体与正电子发射计算机断层成像术使检查功能成为可能 局限于皮质和皮质下的改变 结构。在建议的研究中，正电子发射计算机断层扫描使用FMZ 将用于检测BDZ神经递质的密度 大脑皮层和皮质下结构中的受体 PSP患者与正常对照组的比较 研究对象。这些发现将与以下研究相关联 测量局部大脑葡萄糖代谢率(LCMRG) 通过FDG和PET以及认知的定量测试， 运动和语言功能。初步研究表明 在PSP中，FMZ在额叶的结合会减少 大脑皮层区域，但顶叶正常 和枕部区域。这些研究还表明， 绑定的减少将对应于 大脑中脑区的神经心理任务 大脑。

This is a request for continuing support to study the density of gamma-aminobutyric acid (GABA)-A/benzodiazepine neurotransmitter receptors in the central nervous system in the neurodegenerative disease, progressive supranuclear palsy (PSP), and relate the findings to the cognitive and motor disturbances in this disease. Evidence suggests that changes in these receptors may be important in the pathophysiology of this disorder. In PSP the cognitive and movement disorders are thought to result from neuropathological changes in subcortical structures, but positron emission tomography (PET) studies with [18F]fluorodeoxyglucose (FDG) demonstrate widespread hypometabolism in the central nervous system (CNS), including the cerebral cortex. This raises the possibility that the cognitive disorders result from cerebral cortical and not subcortical pathology. The development of a ligand, [11C]flumazenil (FMZ), to study gamma-aminobutyric acid (GABA)-A/benzodiazepine (BDZ) neurotransmitter receptors with PET makes it possible to examine functional alterations localized to cortical and subcortical structures. In the studies proposed, PET scans with FMZ will be used to examine the density of BDZ neurotransmitter receptors in the cerebral cortex and subcortical structures in patients with PSP as compared with normal control subjects. The findings will be correlated with studies of local cerebral metabolic rates for glucose (LCMRG) measured with FDG and PET and with quantitative tests of cognitive, motor and speech function. Preliminary studies suggest that in PSP, FMZ binding will be decreased in the frontal regions of the cerebral cortex but normal in the parietal and occipital regions. These studies also suggest that the decrease in binding will correspond to performance on neuropsychological tasks mediated by this region of the brain.