BENZODIAZEPINE RECEPTORS IN NEURODEGENERATIVE DISEASES

这是要求继续支持研究 γ-氨基丁酸（GABA）-A/苯二氮卓类药物密度 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 运动障碍 证据表明 这些受体的变化可能是重要的 这种疾病的病理生理学。 在PSP中，认知和运动障碍被认为 皮质下的神经病理学变化 结构，但正电子发射断层扫描（PET）研究 [18F]氟脱氧葡萄糖（FDG）的研究表明， 中枢神经系统（CNS）中的代谢减退， 包括大脑皮层 这就提出了一种可能性， 认知障碍是由大脑皮层 而不是皮层下病变 的发展 配体，[11 C]氟马西尼（FMZ），研究γ-氨基丁酸 酸（GABA）-A/苯二氮卓类（BDZ）神经递质 受体与PET使得有可能检查功能 皮质和皮质下改变 结构. 在提出的研究中，使用FMZ进行PET扫描 将用于检测BDZ神经递质的密度 大脑皮层和皮层下结构中的受体 PSP患者与正常对照组比较 科目 这些发现将与以下研究相关联： 测量局部脑葡萄糖代谢率（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结合将在额叶中减少， 但顶叶正常 和枕骨区域。 这些研究还表明， 结合力的下降将与性能相对应 神经心理学的任务由这个区域的介导 个脑袋

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.