Aerobic Exercise, Neurotrophins, and fMRI of Hippocampal Function and Structure

描述（由申请人提供）：本Pathways赠款中提出的研究确定并寻求填补目前关于有氧运动与心血管健康以及人类大脑功能和结构健康之间关系的知识空白。拟议中的人类神经成像研究建立在大量现有动物研究的基础上，旨在将这项工作扩展到人类。候选人有兴趣建立一个独立的研究生涯，她可以研究有氧运动和心血管健康对人类认知和大脑健康的影响。候选人过去和现在的研究包括功能性磁共振成像（fMRI）研究工作记忆和长期记忆之间的相互作用，以及内侧颞叶（包括海马）和前额叶皮层在工作记忆中的作用。该计划的总体目标是为候选人在转化认知神经科学领域的独立科学家职业生涯做好准备。导师包括Chantal E. Stern，D.Phil.，记忆的认知神经成像专家，罗伯特·C。Wagenaar博士，运动生理学和神经康复学教授，以运动障碍方面的研究而闻名。Budson，医学博士，认知和行为神经学专家，他以研究阿尔茨海默病的认知功能障碍和记忆功能障碍而闻名，他是临床心理学教授和衰老神经心理学专家。该研究计划的目标是：1）使用两种记忆任务和功能磁共振成像，在有氧运动、心血管健康、大脑依赖性记忆的功能神经解剖学和神经营养因子--脑源性神经营养因子（BDNF）之间建立联系（具体目标#1），2）调查健康的年轻人和久坐不动的老年人12周的有氧运动干预是否与记忆任务表现的改善有关，使用fMRI和前测-后测随机对照组设计，增加血清BDNF水平，增强任务相关海马活动（具体目标#2），和3）研究在健康的年轻和年长的久坐个体中相同的有氧运动干预是否导致海马和/或海马子区的体积增加，以及其他脑区的皮质厚度。候选人将获得运动生理学和神经康复，老年神经病学，临床神经心理学评估，结构MRI图像的形态测量分析以及临床试验设计方面的基本培训。该项目将使候选人能够建立一个外部资助的转化认知神经科学研究计划。有氧运动可能是一种有效和低成本的干预措施，不仅促进身体健康，而且促进大脑健康，从而实现健康老龄化。定期中等强度的有氧运动可能在整个生命周期中具有神经保护作用。 公共卫生相关性：定期中等强度的有氧运动可能是一种有效和低成本的健康老龄化干预措施，不仅促进身体健康，而且促进大脑健康，并可能在整个生命周期中具有神经保护作用。运动对大脑的这些影响已经在动物模型中得到了广泛的研究，但在人类中还没有。这组研究旨在研究健康的年轻人和老年人的衰老，运动和大脑之间的关系。

DESCRIPTION (provided by applicant): The research proposed in this Pathways grant identifies and seeks to fill a current gap in knowledge regarding the relationship between aerobic exercise and cardiovascular fitness and functional and structural brain health in humans. The proposed human neuroimaging studies build upon a large body of existing animal research, and aim to extend this work to humans. The candidate is interested in establishing an independent research career in which she can study the effects of aerobic exercise and cardiovascular fitness on cognition and brain health in humans across the lifespan. The candidate's past and current research has included functional Magnetic Resonance Imaging (fMRI) studies of interactions between working memory and long-term memory and the role of the medial temporal lobes (including the hippocampus) and prefrontal cortex in working memory. The overall goal of this proposal is to prepare the candidate for a career as an independent scientist in translational cognitive neuroscience. Mentors include Dr. Chantal E. Stern, D.Phil., an expert in the cognitive neuroimaging of memory, Dr. Robert C. Wagenaar, Ph.D., a professor of exercise physiology and neurorehabilitation who is known for his work on movement disorders, Dr. Andrew E. Budson, M.D., an expert in cognitive and behavioral neurology, who is known for his work on cognitive dysfunction and memory dysfunction in Alzheimer's Disease, and Dr. Alice Cronin-Golomb, Ph.D. a professor of clinical psychology and an expert in the neuropsychology of aging. The goals of the research plan are to 1) establish a link between aerobic exercise, cardiovascular fitness, the functional neuroanatomy of hippocampal-dependent memory, and a neurotrophin, the Brain-Derived Neurotrophic Factor (BDNF) in humans using two memory tasks and fMRI (Specific Aim #1), 2) investigate whether a 12-week aerobic exercise intervention in healthy young and older sedentary adults is associated with an improvement in memory task performance, increased serum BDNF levels, and enhanced task-related hippocampal activity using fMRI and a pretest-posttest randomized control group design (Specific Aim #2), and 3) investigate whether the same aerobic exercise intervention in healthy young and older sedentary individuals results in increased volume in the hippocampus and/or hippocampal subfields, and cortical thickness in other brain areas using structural MRI and morphometric methods. The candidate will acquire essential training in exercise physiology and neurorehabilitation, geriatric neurology, clinical neuropsychological assessment, morphometric analyses of structural MRI images, and in clinical trial design. The project will enable the candidate to establish an externally funded research program in translational cognitive neuroscience. Aerobic exercise may be an effective and low-cost intervention resulting in healthy aging by promoting not only physical health, but also brain health. Regular moderate intensity aerobic exercise may have neuroprotective effects throughout the lifespan. PUBLIC HEALTH RELEVANCE: Regular moderate intensity aerobic exercise may be an effective and low-cost intervention for healthy aging by promoting not only physical health, but also brain health, and may have neuroprotective effects throughout the lifespan. These effects of exercise on the brain have been studied extensively in animal models, but not in humans. This set of studies aims to examine the relationship between aging, exercise, and the brain in healthy young and older individuals.