Abstract

Project Title – Effects of Metyrapone on Alzheimer’s Disease Pathology in Rats
Mentor – Jennifer Yates

Alzheimer’s Disease (AD) is a type of dementia affecting millions of people worldwide, and only symptomatic treatments are currently available. The hallmark pathological characteristics of AD are intracellular neurofibrillary tangles and extracellular plaques. The symptoms include progressive memory loss, disorientation in behavior, and mood disorders. Results of recent studies suggest that depression may not only be a symptom of AD, but it may also have a role in the onset or progression of the disease. Depression is also associated with impairment in cognitive function, which is also seen in AD patients. Depression is associated with a disturbance in the hypothalamic-pituitary-adrenal axis, which results in an increase in the secretion of glucocorticoids. This disturbance can also be caused by stress, which is why stress is considered to be a trigger of depressive episodes. Previous studies have shown that artificial administration of stress-level glucocorticoids leads to an increase in plaque formation, as well as accelerating the formation of neurofibrillary tangles. It has also been shown that treating high glucocorticoid levels with a glucocorticoid antagonist drug slows down the progression of the disease. A therapeutic drug used in the treating people with high glucocorticoid levels is metyrapone. For this study, Sprague-Dawley rats were exposed to chronic stress using rodent immobilization bags, while being treated with metyrapone. Their cognitive function was measured using the Barnes Maze. Results of this test revealed that there was no significant difference in cognitive performance that could be attributed to metyrapone treatment. To see whether there was an impact on the cellular and molecular level, further immunohistochemical analysis is necessary to quantify plaque and neurofibrillary tangle formation.