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2018 USRA Book of Abstracts 18.pdf

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Faculty Advisors

Krebs, Robert

Description

PURPOSE: Accumulating evidence indicates a potential link between activity of enzyme Cytochrome P450-46A1 (CYP46A1) in the brain and neurodegenerative Alzheimer’s disease. Past research, using low doses of efravirenz treatment on 5xFAD mice to activate CYP46A1CYP46A1 showed two significant trends: an increased level of Plasma 24-hydroxycholesterol and decreased Alzheimer’s pathological hallmarks such as amyloid, amyloid precursor protein and behavioral symptoms. This study was designed to measure sterol precursor levels in the brain of rats treated with (-)-P7C3- S243, observing the activity of CYP46A1 as a pharmacologic target of Alzheimer’s disease. METHODS: The homogenate brain samples analyzed were TgF344-AD rats, a wellcharacterized preclinical Alzheimer’s model by isolation isotope dilution gas chromatography-mass spectrometry. RESULTS: The statistical relevance found was that cholesterol levels of vehicletreated rats, were lower in 15-month-old models than in 24-month-old models. Female diseased rats had higher desmosterol levels than males. Younger male wild-types possessed higher cholesterol and desmosterol levels than diseased rats. CONCLUSIONS: There was no clear indication of a link of biological pathways between CYP46A1 activity and administration of neuroprotective agent (-)-P7C3- S243. However, results corroborated past findings in 5xFAD knockout mice; cholesterol levels were lower in younger rats due to developmental causes.

Publication Date

2018

College

College of Sciences and Health Professions

Department

Biological, Geological, and Environmental Sciences

Student Publication

This item is part of the McNair Scholars Program.

Changes in Sterol Patterns of Rat Alzheimer’s Models in Response to Administration of Neuroprotective Compound (-)-P7C3-S243

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