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: 3084068
• 负责人: MARK Jay ALBERTS
• 金额: $ 7.21万
• 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/3084068
• 关键词: Alzheimer's disease; brain mapping; human tissue; immunochemistry; immunocytochemistry; immunologic techniques; in situ hybridization; neuroanatomy; neurotrophic factors; 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）是痴呆症最常见的原因 在美国。 其病理和生化特征之一 AD是脑中胆碱能神经元的损失。 神经生长 神经生长因子（NGF）对胆碱能神经元具有营养特性， 某些情况下。 最近在大鼠中检测到NGF 大脑和有一个区域分布密切平行的 大脑中的胆碱能神经支配 NGF被以下细胞摄取： 胆碱能神经元和转运逆行到核 Meynert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。 主要 这个培训和发展项目的假设是， NGF生产、运输或利用的改变可能会导致 在AD发病机制中的作用。 具体目标是 项目是（1）确认NGF在人体内的存在， （2）确定NGF在脑内的区域分布; 人脑，和（3）比较正常和 AD大脑，如果发现差异，确定它们是否是由于 NGF生产、运输或利用的改变。 人脑标本将通过快速 尸检方案。 通过北方印迹检测NGF， 免疫细胞化学 NGF的定量将通过点- 印迹和酶联免疫测定，以及原位杂交 将用于确定区域和细胞定位。 所有 上述技术将被用来探索差异， 正常与AD脑组织中NGF含量及分布的比较。 如果 发现了显著差异，它们可能对 了解AD的病因并制定治疗方案。