Aminergic Function in Aging and Alzheimers Disease

衰老和阿尔茨海默病中的胺能功能

• 批准号: 6323971
• 负责人: PAULA C BICKFORD
• 金额: $ 103.02万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-03-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6323971
• 关键词: Alzheimer's disease; aging

DESCRIPTION: This program project grant is focused on understanding the physiological and biochemical alterations in the brain underlying changes in cognition during aging and Alzheimer's disease. There are several themes that weave throughout the program project. The first theme is to examine the role of oxidative stress in aging. Projects 13, 15, 4 and 16 will continue their collaboration regarding nutritional interventions with diets high in antioxidants. Thus we will extend our studies of interventions with antioxidants to LTP and also possible synergy with neurotrophins. A new theme for the renewal that threads through our program is the investigation of inflammatory processes in aging and its relation to oxidative stress. Project 13 and Project 4 have examined a line of rats resistant to oxidative stress that has an increased life span and does not show age-related declines in cerebellar physiology and motor learning, or age-related atrophy of basal forebrain cholinergic neurons. These rats have a deficiency in a microglial cell adhesion molecule (LFA-l), indicating reduced inflammation in aging, and a reduction in reactive oxygen species (ROS). The role of inflammation will be studied from a therapeutic angle in Project 14 looking at NSAIDS and specific COX-2 inhibitors. A third theme is related to biological substrates of age-related changes in cellular models for learning and memory, such as long-term potentiation (LTP). Projects 15 and 4 will examine trophic factor interactions with LTP, using intraocular transplants of hippocampus at different ages and denervation and NGF treatment as paradigms for NGF release. Project 3 will investigate PKA-dependent synthesis of AMPA receptors, and the transcriptional regulation of AMPA receptors by trophic factors will be examined in Project 16. Project 13 will examine alterations in PKA with age that will relate to these projects as well. Another focus of our program is age-related alterations of the basal forebrain cholinergic system; nicotinic receptors are studied in Project 14 and neurotrophic support in Project 4. Our particular strength is the multidisciplinary approach in our different research groups, from the whole animal behavior to single cell recording, morphology, and biochemical assays of protein levels. The long-term goal of our program is to understand the basic biological mechanisms of aging and cognition that will lead to new therapies for Alzheimer's disease and other age-related cognitive diseases.

描述：该计划项目赠款的重点是了解 生理和生物化学的变化，在大脑中的变化， 老年痴呆症和老年痴呆症之间的关系。有几个主题， 贯穿整个项目的始终。第一个主题是审视 氧化应激在衰老中的作用项目13、15、4和16将继续其 在营养干预方面开展协作， 抗氧化剂因此，我们将扩展我们的干预研究， 抗氧化剂的LTP，也可能与神经营养因子的协同作用。一个新的主题 在我们的节目中贯穿的是对 衰老中的炎症过程及其与氧化应激的关系。项目 13和项目4研究了一系列抗氧化应激的大鼠 寿命延长，并且没有表现出与年龄相关的下降， 小脑生理学和运动学习，或年龄相关的基底节萎缩， 前脑胆碱能神经元这些老鼠缺乏小胶质细胞 细胞粘附分子（LFA-1），表明衰老中炎症减少，和 减少活性氧（ROS）。炎症的作用将 在项目14中从治疗角度研究NSAIDS， 特异性考克斯-2抑制剂。第三个主题与生物基质有关 与年龄相关的学习和记忆细胞模型的变化，如 长时程增强（LTP）。项目15和4将研究营养因子 与LTP的相互作用，使用海马的眼内移植， 不同年龄和去神经支配和NGF治疗作为NGF释放的范例。 项目3将研究AMPA受体的PKA依赖性合成， 营养因子对AMPA受体的转录调控将是 在项目16中检查。项目13将检查PKA随年龄的变化 这也与这些项目有关。我们节目的另一个重点是 基底前脑胆碱能系统的年龄相关改变;烟碱 受体的研究在项目14和项目4的神经营养支持。我们 特别的优势是多学科的方法，在我们不同的 研究小组，从整个动物行为到单细胞记录， 形态学和蛋白质水平的生化测定。的长期目标 我们的计划是了解衰老的基本生物学机制， 认知，这将导致新的治疗阿尔茨海默病和其他 与年龄相关的认知疾病