Protective effects of exercise against Alzheimer's disease in a transgenic rat model

点击翻译按钮获取中文摘要

ABSTRACT Nearly 6 million Americans suffer from Alzheimer's disease (AD) and that number is expected to rise to 14 million by 2050 (1). Currently there is no cure or even a treatment to slow its progression, however, exercise has proven to reduce your risk (5-9,60,61). Several studies have linked exercise to improved cognition and increased brain volume in AD (10,62-64). This project will shed light on the mechanisms behind this protection, to not only promote exercise as a preventative tool but to also unveil potential pathways for pharmacological intervention in those patients unable to exercise. Two mainstream hypotheses exist for the exercise-induced protection against AD. One is that exercise increases brain-derived neurotrophic factor (BDNF) which plays a role in promoting brain plasticity and long-term potentiation (65). The second is that exercise protects against AD by reducing the development of plaque (amyloid-β) and tangles (tau protein). Due to the nature and complexity of the disease, researching a cure or treatment has been difficult. However, a rat strain has recently been developed (TgF344-AD) that displays a complete repertoire of AD pathological features, including, age- dependent accumulation of cerebral amyloid-β that preempts tauopathy, cognitive disturbance, apoptosis, and neuronal loss (66). This strain will be key to the greater understanding of the human disease. With this project, I plan to 1) establish a timeline of the exercise-induced protect against AD in this novel transgenic model of AD and 2) shed light on the mechanisms of protection. To accomplish this, TgF344-AD animals will be bred at Boise State University. Following genotyping, they will be placed in either an AD or wild type group. Additionally, they will be divided into either sedentary or exercise group. While the sedentary group will be restricted to cage activity, the exercise group will be treadmill trained 5 days per week for 6 months. Every 3 months from birth to 18 months, all animals will be assessed for memory, coordination and muscular strength. At 18 months of age, brain, skeletal muscle, cerebrospinal fluid and blood will be harvested and biochemical analysis will be conducted. Among the proposed analyses, we will measure FNDC5/Irisin in all the tissues. This is an important project that will provide valuable information to researchers working with this novel model of AD. In addition, it will determine the role of FNDC5/Irisin pathway in the exercise-induced neuroprotection. This project will serve as a significant step in the fight against Alzheimer's disease.