NEUROBEHAVIOR NEUROCHEMISTRY AND NEUROPATHOLOGY OF OPCA

我们提案的长期目标是了解 神经行为改变的生理学和病因学基础 显性遗传性橄榄体桥脑小脑萎缩（OPCA）患者，a 小脑性共济失调 这将通过以下方式实现： 神经行为和脑神经化学和神经病理学检查 来自五个美国OPCA家庭的30名患者。 我们的四个具体目标 跨学科研究如下： 1)了解大脑胆碱能系统在OPCA中的作用， 小脑在认知缺陷的典型患者额叶 叶瓣损伤; （二） 为兴奋性氨基酸提供生物化学解释， OPCA脑内磷脂代谢物的变化; 第三章 调查"回退"现象的可能性， OPCA黑质纹状体多巴胺神经元 四、 通过吞咽困难改善OPCA患者的生活质量 干预 我们的建议的特点包括独特的能力， 的申请人前瞻性和仔细地跟踪病人从五个 美国OPCA家庭每年进行一次神经行为评估，直到尸检， 以及每个申请人在相关领域的专业知识 神经行为评估、吞咽困难干预和人脑 神经化学和神经病理学技术。 我们建议 要获得的信息本身对于表征 疾病的各个方面相对被忽视， 科学界，更普遍地说，可能会导致新的 大脑行为相关性与我们对正常 和异常的大脑功能

The LONG-TERM GOAL of our proposal is to understand both the physiologic and etiological bases of the neurobehavioural changes of patients with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder. This will be accomplished through neurobehavioural and brain neurochemical and neuropathological examination of 30 patients from five U.S. OPCA families. The four specific aims of our interdisciplinary study are the following: 1) to understand in OPCA the role of the brain cholinergic system and the,cerebellum in the cognitive deficits typical of patients with frontal lobe damage; 2) to provide a biochemical explanation for the excitatory amino acid and phospholipid metabolite changes in OPCA brain; 3) to investigate the possibility of a "dying-back" phenomenon involving the OPCA nigrostriatal dopamine neurone; and 4) to improve the quality of life of our OPCA patients through dysphagia intervention. The SPECIAL FEATURES of our proposal include the unique ability of the applicants to follow prospectively and carefully patients from five U.S. OPCA families with annual neurobehavioural assessment until autopsy, and the demonstrated expertise of each of the applicants in the relevant neurobehavioural assessment, dysphagia intervention, and human brain neurochemical and neuropathological techniques. We suggest that the information to be obtained is important in its own right for characterizing aspects of a disorder which have been relatively neglected by the scientific community and, more generally, is likely to lead to new brain-behavioural correlations relevant to our understanding of both normal and abnormal brain functioning.