Date of Award

Spring 4-10-2025

Embargo Period

4-22-2025

Document Type

Thesis

Degree Name

Master of Biomedical Science

College

College of Graduate Studies

First Advisor

Robin Muise-Helmericks

Second Advisor

Adviye Ergul

Third Advisor

Jeffrey Jones

Fourth Advisor

Takako Makita

Abstract

Adequate cerebral perfusion is necessary to help the brain maintain a constant and steady state of nutrient delivery. Since the brain is highly metabolic, changes in the vasculature structure can impact perfusion levels and, therefore, reduce the ability of the brain to receive the support necessary for full functionality. Vascular dysfunction is a common comorbidity among obese individuals. Given the strong association between obesity and cognitive dysfunction, understanding the correlation between reduced cerebral perfusion and altered cerebrovascular structure is crucial. The overall hypothesis of this thesis originated after ample preliminary data, and states that diet-induced obesity reduces cerebral perfusion and alters the structural parameters of vasculature in the hippocampal region, contributing to cognitive decline.

To test our hypothesis, we assessed brain vasculature and perfusion levels in a murine model of diet-induced obesity following 6-24 weeks of either a standard or high-fat diet. We performed IHC leptin staining and utilized Zeiss 880 confocal microscopy to image the hippocampal region for quantification of branching points. Laser speckle imaging was used to measure perfusion levels, where changes were analyzed in PIMsoft software. After 24 weeks of diet in female mice, a high-fat diet significantly reduced perfusion in specific brain regions, with all regions showing a downward trend in perfusion levels. Male mice exhibited negative trends of perfusion levels in all regions after 24 weeks of a high-fat diet. A significantly higher number of branching points were found after 6 weeks of diet. However, after 24 weeks of diet, the standard diet mice maintained more branching points, suggesting that high-fat diet mice experience an unsustainable compensation mechanism that fails long term, while healthy mice sustain consistent levels.

Rights

Copyright is held by the author. All rights reserved.

Download

Share

COinS