Exercise and the Aged Brain: Neurotrophins and Stress

描述(由申请人提供)：为本地区公民的平均年龄 美国每年都在随着婴儿数量的增加而增加 婴儿潮一代达到退休年龄，患有 与年龄相关的神经问题增加。例如，据估计， 如果没有有效的治疗方法，就会开发预防性的方法或治疗方法 对于阿尔茨海默病(AD)来说，AD患者的数量将超过 在接下来的40-50年内翻两番。其他与年龄相关的障碍，如 帕金森氏症、抑郁和学习记忆全面下降 这一进程将显示出类似的大幅增加的患病人数。 拟议的区域项目使用动物模型来解决这个问题，方法是 描述体育锻炼对大鼠大脑的影响，特别是 论内源性生化对营养和营养的影响 维持神经元、神经营养因子的整体健康。该项目将是 在科罗拉多大学丹佛分校(UCD)进行的，这是一个城市 为许多非传统学生提供服务的大学，培养了重要的人才 从事生物医学科学职业的毕业生人数，而不是 NIH支持的主要接受者。这一地区的项目利用老年老鼠，一只 已经被广泛研究的人类衰老的动物模型与 衰老时出现的认知功能下降。中以前的报告 文献已发现，在幼年或中年大鼠中进行自愿运动 提高神经营养素的mRNA水平。然而，目前还没有发布任何报告 研究运动对老年大鼠脑的影响。具体目标1旨在 测定运动是否增强老年大鼠脑内神经营养素的表达 系统检测运动性神经变化的时间进程 生长因子和脑源性神经营养因子的mRNA和 蛋白质表达。具体目标2将评估自愿的压力水平 对比强迫体育锻炼对不同年龄的大鼠造成的影响，以及这是如何 影响NGF和BDNF的表达。具体目标3将测试 运动对老年大鼠学习记忆任务的影响及其相关性研究 脑内神经营养素水平与行为表现的关系。未来研究 将测试体育锻炼对脑内神经营养因子表达的影响 脑和关于与年龄相关的神经疾病的动物模型 人类，内源性神经营养因子水平的上调可能是 有治疗作用。可能的疾病包括帕金森氏症和抑郁症。 该项目将建立一个新的和富有成效的研究计划，将 为UCD学生提供更多的研究机会。

DESCRIPTION (provided by applicant): As the average age of citizens in the United States increases each year with the large number of people from the baby boomer generation reaching retirement age, the number of patients with age-associated neurological problems increases. For example, it is estimated that if no effective treatments, preventative approaches or cures are developed for Alzheimer's disease (AD), that the number of AD patients will more than triple in the next 40-50 years. Other age related disorders, such as Parkinson's disease, depression and overall decline in learning and memory processes will show similar dramatic increases in number of people afflicted. The proposed AREA project uses an animal model to address this issue by characterizing the effects of physical exercise on the rat brain, in particular on the expression of endogenous biochemical's responsible for nourishing and maintaining the overall health of neurons, neurotrophins. The project will be conducted at the University of Colorado at Denver (UCD), which is an urban university that serves many non-traditional students, trains significant numbers of graduates who pursue careers in the biomedical sciences, and is not a major recipient of NIH support. This AREA project utilizes the aged rat, an animal model for human aging that has been extensively studied in relation to the decline in cognitive function seen in senescence. Previous reports in the literature have found that voluntary exercise in young or middle aged rats enhances neurotrophin mRNA levels. However, no reports have been published studying exercise effects in the aged rat brain. Specific Aim 1 seeks to determine if exercise enhances neurotrophin expression in the aged rat brain by systematically examining the time course of exercise induced changes in nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) mRNA and protein expression. Specific Aim 2 will assess the level of stress voluntary versus forced physical exercise causes in rats of various ages, and how this impacts NGF and BDNF expression. Specific Aim 3 will test the effect of exercise on learning and memory tasks in the aged rats and seeks to correlate neurotrophin levels in the brain with behavioral performance. Future studies will test the impact of physical exercise on neurotrophin expression in the brain and on animal models of age-associated neurological disorders found in humans, in which up regulation of levels of endogenous neurotrophins may be therapeutic. Possible disorders include Parkinson's disease and depression. This project will establish a new and productive research program that will provide increased research opportunities for UCD students.