Effect of dietary restriction and exercise on behavioral outcomes and brain pathology in a transgenic model of Alzheimer's disease

饮食限制和运动对阿尔茨海默病转基因模型行为结果和脑病理学的影响

• 批准号: 10657756
• 负责人: Stephanie E Hall
• 金额: $ 25.27万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657756
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Alzheimer' s disease therapy; American; Amyloid beta-Protein; Animal Disease Models; Animal Diseases; Animal Model; Antioxidants; Apoptosis; Autophagocytosis; Behavior; Behavioral; Brain; Brain Pathology; Caloric Restriction; Cause of Death; Cells; Cerebrum; Cognitive; Computer Models; Diagnosis; Disease; Elderly; Energy Intake; Exercise; Impaired cognition; Inflammation; Intermittent fasting; Intervention; Learning; Link; Literature; Measurement; Measures; Memory; Methods; Mission; Modeling; Molecular; Muscle; Neurobiology; Neurofibrillary Tangles; Neuronal Plasticity; Neurons; Oxidative Stress; Pathologic; Pharmacologic Substance; Pharmacological Treatment; Phase; Physiological; Process; Race; Rat Strains; Rat Transgene; Rattus; Risk; Risk Reduction; Senile Plaques; Skeletal Muscle; Tauopathies; Therapeutic; Therapeutic Intervention; Time; Tissues; abeta accumulation; age related; behavior influence; behavioral outcome; brain health; compliance behavior; cost; diet and exercise; dietary restriction; hyperphosphorylated tau; improved; inflammatory marker; innovation; interest; neurogenesis; neuron loss; neuroprotection; neuroregulation; novel; oxidative damage; preempt; protective effect; protective pathway; tau Proteins; transgenic model of alzheimer disease; treatment planning

PROJECT SUMMARY: HALL PROJECT Alzheimer’s Disease (AD) is one of the most devastating diseases of our time; with nearly 6 million diagnosed it ranks as the third leading cause of death among older adults. In the race for a cure one thing is certain—diet and exercise reduce risks. However, the mechanisms responsible for the reduced risks are unknown. Several studies have linked dietary restriction and exercise to improved memory, reduced amyloid beta plaques, and tau protein tangles in AD. This project will evaluate if intermittent fasting (IF), a popular method of dietary restriction, administered independently and in combination with exercise, is neuroprotective in a novel model of AD, the TgF344-AD transgenic rat. The aims of this project are three-fold. 1) To characterize IF protective effects on behavioral outcomes (memory, coordination, and strength) in the TgF344-AD rat. 2) To determine if exercise provides additional protection when combined with IF. 3) To assess the effects of IF independent and in combination with exercise on AD pathology and protective pathways of interest. This project will result in an unveiling of the effect of IF in the brain and skeletal muscles tissue in the TgF344-AD animal and project could establish a pathway of protection for future research into pharmacological treatment of this devastating disease.

项目概要：大厅项目 阿尔茨海默病（AD）是我们这个时代最具破坏性的疾病之一;有近600万人被诊断出患有AD。 它是导致老年人死亡的第三大原因。在寻找治愈方法的竞赛中，有一件事是肯定的--饮食 锻炼可以降低风险。然而，导致风险降低的机制尚不清楚。几 研究表明，饮食限制和锻炼与改善记忆、减少淀粉样蛋白β斑块以及 AD中的tau蛋白缠结。该项目将评估间歇性禁食（IF），一种流行的饮食方法， 在一个新的模型中，限制，单独给药和与运动结合，是神经保护性的。 AD，TgF 344-AD转基因大鼠。该项目的目标有三个方面。1)表征IF保护 对TgF 344-AD大鼠行为结果（记忆、协调和力量）的影响。2)以确定是否 当与IF结合时，运动提供额外的保护。3)评估IF独立和 结合对AD病理学和感兴趣的保护途径的锻炼。该项目将导致 揭示IF在TgF 344-AD动物的脑和骨骼肌组织中的作用， 建立一个保护的途径，为未来的研究药物治疗这一毁灭性的 疾病