Exercise and the Aged Brain: Neurotrophins and Stress

描述（由申请人提供）：由于公民的平均年龄在 美国每年都有大量的婴儿随着人口的增加而增加 婴儿潮一代达到退休年龄， 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，预防方法或治疗方法被开发出来， 对于阿尔茨海默病（AD），AD患者数量将超过 在接下来的40 - 50年里翻三倍。其他与年龄有关的疾病，如 帕金森病、抑郁症和学习记忆力的整体下降 过程将显示类似的患病人数急剧增加。 拟议的区域项目使用动物模型来解决这个问题， 描述体育锻炼对大鼠大脑的影响，特别是 内源性生物化学的表达负责滋养和 维持神经元和神经营养素的整体健康。该项目将 在丹佛的科罗拉多大学（UCD）进行，这是一个城市 一所为许多非传统学生服务的大学，培养了重要的 追求生物医学科学职业的毕业生人数， 是NIH资助的主要对象该区域项目利用老年大鼠， 人类衰老的动物模型，已被广泛研究， 衰老时认知功能的下降。以前的报告 文献发现，青年或中年大鼠的自愿运动 增强神经营养因子mRNA水平。不过，目前尚未公布任何报告 研究运动对老年大鼠大脑的影响。具体目标1： 通过以下方法确定运动是否能增强老年大鼠大脑中神经营养因子的表达： 系统地检查运动引起的神经变化的时间过程， 脑源性神经营养因子（BDNF）mRNA， 蛋白质表达具体目标2将评估自愿的压力水平 与强迫性体育锻炼相比，在不同年龄的大鼠中， 影响NGF和BDNF的表达。具体目标3将测试的效果 运动对老年大鼠学习和记忆任务的影响，并试图将其与 神经营养素水平与行为表现的关系未来的研究 将测试体育锻炼对神经营养因子表达的影响， 大脑和年龄相关的神经系统疾病的动物模型， 人类，其中内源性神经营养因子水平的上调可能是 有治疗作用的可能的疾病包括帕金森病和抑郁症。 该项目将建立一个新的和富有成效的研究计划， 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.