NGF-RESPONSIVENESS AND AMYLOID GENE EXPRESSION IN ALZHEIMER'S DISEASE

阿尔茨海默病中的 NGF 反应性和淀粉样蛋白基因表达

• 批准号: 3726527
• 负责人: GERALD A HIGGINS
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3726527
• 关键词: Alzheimer's disease; aging; amyloid proteins; brain septal area; cholinergic receptors; gene expression; genetic transcription; growth factor receptors; human tissue; immunocytochemistry; in situ hybridization; mesencephalon; messenger RNA; molecular pathology; neural plasticity; neurotrophic factors; polymerase chain reaction; postmortem; prosencephalon; substantia innominata

This project addresses the question of whether deficits in NGF- responsiveness may underly some of the neuropathological changes which occur in the basal forebrain in Alzheimer's disease (AD). We propose to test the hypothesis that expression of the nerve growth factor (NGF-R) gene is a sensitive indicator of the morphological integrity of basal forebrain cholinergic neurons (Ch1 - Ch4) cell groups), with increased levels of NGF-R mRNA and neuronal hypertrophy correlated with high levels of NGF in cortical target regions, and decrease levels of NGF-R and neuronal atrophy correlated with growth factor deprivation. In situ hybridization of NGF-R mRNA will be combined with quantitative measures of cell number and cellular hybridization intensity to document changes in NGF-R gene expression within components of the Ch1-Ch4 cell groups in AD. One mechanism by which amyloid deposition may occur with cortical target regions is by changes in the expression of the amyloid protein precursor (APP) gene within cortically-projecting cholinergic neurons of the basal forebrain. Thus, we will test the hypothesis that a specific form of APP mRNA transcript may be preferentially correlated with decreased NGF- responsiveness in Alzheimer's disease. These experiments will combine in situ hybridization methods with recently developed reverse transcriptase- polymerase chain reaction (R-PCR) to provide relative quantification of changes in the ratios of APP mRNA in AD.

该项目解决了是否在神经生长因子赤字的问题- 反应性可能是某些神经病理学变化的基础， 发生在阿尔茨海默病（AD）的基底前脑。我们建议 检验神经生长因子（NGF-R）的表达 基因是一个敏感的指示器的形态完整性， 前脑胆碱能神经元（Ch 1-Ch 4）细胞组），增加 NGF-R mRNA水平和神经元肥大与高水平 皮质靶区的NGF，并降低NGF-R和 神经元萎缩与生长因子剥夺相关。 原位 NGF-R mRNA的杂交将与以下定量测量相结合： 细胞数量和细胞杂交强度，以记录 AD中Ch 1-Ch 4细胞组成分内NGF-R基因表达 皮质靶向淀粉样蛋白沉积可能发生的一种机制 区域是通过淀粉样蛋白前体表达的变化 (APP)基底节皮质投射胆碱能神经元内的基因 前脑 因此，我们将检验一种特定形式的APP mRNA转录物可能优先与减少的NGF相关。 阿尔茨海默病的反应性。 这些实验将联合收割机 原位杂交方法与最近开发的逆转录酶- 聚合酶链反应（R-PCR），以提供 APP mRNA在AD中的比例变化。