ROLE OF NERVE GROWTH FACTOR IN ALZHEIMER'S DISEASE

神经生长因子在阿尔茨海默病中的作用

• 批准号: 3084071
• 负责人: MARK Jay ALBERTS
• 金额: $ 7.58万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084071
• 关键词: Alzheimer's disease; brain mapping; human tissue; immunochemistry; immunocytochemistry; immunologic techniques; in situ hybridization; neuroanatomy; neurotrophic factors; northern blottings; substantia innominata

Alzheimer's disease (AD) is the most common cause of dementia in the U.S.. One of the pathologic and biochemical features of AD is a loss of cholinergic neurons in the brain. Nerve growth factor (NGF) has trophic properties on cholinergic neurons under certain circumstances. NGF has been detected recently in rat brains and has a regional distribution which closely parallels the cholinergic innervation in the brain. NGF is taken up by cholinergic neurons and transported retrogradely to the nucleus basalis of Meynert. These findings imply a role for NGF in supporting the cholinergic neurons of the rat brain. The major hypothesis of this training and development project is that alterations in NGF production, transport, or utilization may have a role in the pathogenesis of AD. The specific aims of this project are (1) to confirm the presence of NGF in the human brain, (2) to determine the regional distribution of NGF in the human brain, and (3) to compare NGF levels between normal and AD brains, and if differences are found, determine if they are due to alterations of NGF production, transport, or utilization. Human brain specimens will be obtained through the Rapid Autopsy Protocol. NGF will be detected by Northern blots and immunocytochemistry. Quantitation of NGF will be done by dot- blots and enzyme-linked immunoassays, and in-situ hybridization will be used to determine regional and cellular localization. All of the above techniques will be used to explore differences in NGF content and distribution between normal and AD brains. If significant differences are found, they may have implications for understanding the etiology of AD and planning therapy.

阿尔茨海默病(AD)是导致痴呆的最常见原因 在美国。该病的病理和生化特征之一 AD是指大脑中胆碱能神经元的丧失。神经生长 神经生长因子(NGF)对胆碱能神经元的营养作用 在某些情况下。最近在大鼠体内检测到NGF 并有一个区域分布，这与 大脑中的胆碱能神经支配。NGF由 胆碱能神经元及其逆行转运至核内 迈纳特基底肌。这些发现暗示了NGF在 支持大鼠大脑的胆碱能神经元。少校 这个培训和发展项目的假设是 NGF生产、运输或利用方面的变化可能会 在阿尔茨海默病的发病机制中起作用。这样做的具体目的是 项目有：(1)确认人类体内存在NGF 脑，(2)测定神经生长因子在脑内的区域分布 人脑，以及(3)比较正常和正常的神经生长因子水平 广告大脑，如果发现了差异，确定它们是否 到NGF生产、运输或利用的改变。 人脑样本将通过快速检测获得 验尸协议。NGF将通过Northern blotts和 免疫细胞化学。NGF的定量将以点为单位进行- 印迹和酶联免疫分析及原位杂交 将被用来确定区域和蜂窝定位。全 以上技术的差异将被用来探索 正常和AD脑内神经生长因子的含量和分布。如果 发现了显著的差异，它们可能会对 了解阿尔茨海默病的病因并计划治疗。