EXTRAPYAMIDAL DYSFUNCTION IN NEURODEGENERATIVE DISEASES

这个项目的目标是阐明一些药理作用。 慢性阻塞性肺疾病患者中枢神经系统的变化 橄榄桥小脑萎缩(OPCA)和阿尔茨海默病合并 锥体外系征(AD/EP)。正电子发射断层扫描(PET)将是 用来检测纹状体内突触前单胺能神经元的密度 含[11C]二氢四苯嗪的终末和突触后D2多巴胺能神经元 神经递质受体与[11C]拉氯普利。在患有 锥体外系(EP)运动障碍，这些障碍的强度将 与正电子发射计算机断层扫描研究的结果相关。 我们将检验两个具体的假设。(L)在OPCA患者中，两者 散发性和以遗传为主的形式，纹状体密度 多巴胺能突触前终末和含D2的神经元 相比之下，多巴胺能神经递质受体将减少 与正常对照受试者相比，减少的程度将 预测疾病的未来演变为临床症状 多系统萎缩(MSA)。PET将被用来量化结合 纹状体单胺能突触前终末和纹状体D2 这些患者的神经递质受体与 发育完全的MSA和年龄、性别相近的正常对照组 分配。OPCa患者疾病过程的演变 将在临床上观察以检测那些疾病演变为 MSA，然后在发育之前对这些病例进行PET研究 将MSA与完全发育的患者的PET研究进行比较 MSA、未进展到MSA的OPCA患者和正常对照组 受试者，年龄和性别分布相似。(2)阿尔茨海默氏症 疾病(AD)，EP运动障碍至少部分是由退行性变引起的 含D2多巴胺能神经递质受体的纹状体神经元 而不是纹状体多巴胺能突触前终末的变性， 锥体外系运动障碍的强度直接 与D2多巴胺能受体减少的程度相关。宠物 将用于定量与纹状体单胺能突触前神经元的结合 终末和纹状体D2神经递质受体的表达 伴和不伴锥体外系障碍的AD与正常对照 年龄和性别分布相近的受试者为对照组。纹状体 结合研究将与EP马达的严重程度相关 通过量化的临床运动检查确定的障碍。

The goal of this project is to elucidate some of the pharmacological changes in the central nervous system of patients with olivopontocerebellar atrophy (OPCA) and Alzheimer's disease with extrapyramidal signs (AD/EP). Positron emission tomography (PET) will be used to examine in the striatum the density of presynaptic monoaminergic terminals with [11C]dihydrotetrabenazine and postsynaptic D2 dopaminergic neurotransmitter receptors with [11C]raclopride. In patients with extrapyramidal (EP) motor disorders, the intensity of these disorders will be correlated with the findings in the PET studies. Two specific hypotheses will be tested. (l) In patients with OPCA, both sporadic and dominantly inherited forms, the density of striatal dopaminergic presynaptic terminals and of neurons containing D2 dopaminergic neurotransmitter receptors will be decreased in comparison with those in normal control subjects, and the degree of reduction will predict the future evolution of the disorder into clinically symptomatic multiple system atrophy (MSA). PET will be used to quantify the binding to striatal monoaminergic presynaptic terminals and to striatal D2 neurotransmitter receptors in these patients as compared to patients with fully developed MSA and normal control subjects with similar age and sex distributions. The evolution of the disease process in the OPCA patients will be observed clinically to detect those whose disorders evolve into MSA, then the PET studies of these cases obtained prior to the development of MSA will be compared with PET studies of patients with fully developed MSA, patients with OPCA who do not progress to MSA and normal control subjects, all with similar age and sex distributions. (2) In Alzheimer's disease (AD), EP motor disorders result at least in part from degeneration of striatal neurons containing D2 dopaminergic neurotransmitter receptors and not from degeneration of striatal dopaminergic presynaptic terminals, and the intensity of the extrapyramidal motor disorders is directly correlated with the degree of reduction of D2 dopaminergic receptors. PET will be used to quantify binding to striatal monoaminergic presynaptic terminals and to striatal D2 neurotransmitter receptors in patients with AD with and without extrapyramidal disorders in comparison to normal control subjects with similar age and sex distributions. The striatal binding studies will be correlated with the severity of the EP motor disorders as determined by quantitative clinical motor examinations.