Date of Graduation
Master of Science in Cell and Molecular Biology
Alzheimer’s Disease (AD), amyloid-beta (A), chronic isolation stress, APP/PS1 transgenic mice, exercise training, citrate synthase, COVID-19
Cellular and Molecular Physiology | Exercise Physiology | Molecular and Cellular Neuroscience
Alzheimer’s Disease (AD) is a progressive brain disorder that destroys memory and cognition thought to be initiated through the build-up of the amyloid-beta (A) peptide. The A peptide aggregates, slowly forming into insoluble plaque substances that destroy the brain and worsen patient’s symptoms over time. Studies have shown that chronic isolation stress (CIS) increases the A peptide soluble and insoluble levels in the brain and that exercise training decreases these levels in transgenic mouse models of AD. We sought to determine if an exercise training regimen would rescue the increase in Aβ levels caused by CIS in the APP/PS1 transgenic mouse model of AD. Ninety-six APP/PS1 mice, 48 male and 48 female, were initially assigned to eight groups of twelve. Four groups of male and four female were utilized to assess sex differences in Aβ response. Each sex group was divided into four treatment groups; socially housed sedentary, socially housed exercise trained, CIS sedentary, and CIS exercise trained. Socially housed animals were housed in groups of 4-5 mice in normal size cages. CIS mice were housed alone in cages 1/3 the size of normal cages. Exercise trained mice ran for 60 minutes per day, five days per week, for 10 weeks on a level motor driven treadmill at a speed of 20 m/min. The exercise training regimen began at three months of age. Two-way analysis of variance revealed no sex differences in Aβ levels or exercise training responses so all animals were collapsed into the four treatment groups for further analysis. No differences were found among groups in soleus muscle citrate synthase levels indicating no exercise training effect took place in this study. Insoluble Aβ levels were greater in the CIS sedentary mice than all other groups. The data support the findings of others that CIS results in increased insoluble Aβ levels in AD transgenic mice. The novelfinding of the study is that treadmill running rescues the increase in insoluble Aβ resulting from CIS. Our goal of assessing Aβ production and clearance markers to investigate possible mechanisms for this response was not accomplished due to the lab shutdown by the COVID-19 pandemic.
© Lydia M. Holtmann
Holtmann, Lydia M., "Exercise Training Rescues Increased Brain ISF aβ Caused by Chronic Isolation Stress in APP/PS1 Transgenic Mice" (2021). MSU Graduate Theses. 3644.