Semester

Summer

Date of Graduation

2010

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Bernard G. Schreurs.

Abstract

Recent studies have revealed ambiguous findings on the effects of dietary cholesterol on learning. In one study by Schreurs and coworkers it was reported that a 2% cholesterol diet had a positive effect on learning. However, it was realized that metals, specifically copper, could potentially exacerbate the aggregation of amyloid beta (Abeta), a protein associated with Alzheimer's disease (AD) leading to the formation of Abeta plaques. In a subsequent publication by Sparks and Schreurs it was reported that a 2% cholesterol diet with the addition of 0.12 ppm copper had a detrimental effect on learning and resulted in the formation of Abeta plaques. To better understand the effects of cholesterol and copper on learning and to begin exploring cholesterol's effect on memory we conducted a series of experiments.;In a first study, we investigated the effects of dietary cholesterol and copper on learning. Rabbits fed a diet varying in cholesterol concentration (0, 0.5, 1, and 2%) with 0.12 ppm copper added to the drinking water received Pavlovian conditioning during which levels of learning were assessed. Analysis of Abeta staining, showed a significant cholesterol concentration-dependent increase in the number of Abeta positive neurons in the cortex of the cholesterol-fed rabbits. Learning was significantly greater in the 2% cholesterol-fed rabbits over controls. The data suggested that dietary cholesterol may facilitate learning and memory in the absence of Abeta plaques.;Next, we investigated dietary cholesterol effects on memory retention. We showed that dietary cholesterol had an adverse effect on memory retention of a previously learned task. It is still debatable whether or not dietary cholesterol affects brain cholesterol levels and there are no studies investigating sulfatide levels. Our data suggest that although dietary cholesterol affects memory retention, it does not do so by directly affecting cholesterol or sulfatide levels in the brain, suggesting peripheral effects may be mediated through secondary mechanisms. On the other hand, our data show that brain levels of cholesterol and sulfatides do change as a function of learning and memory.;Finally, in light of these findings, we investigated whether the changes in brain cholesterol and sulfatide levels occurred as a result of a learning task alone and if they occurred quickly or required several months to develop as seen in our previous memory retention experiment. We found significant changes in sulfatide levels as a function of time but no changes as a function of learning in either brain cholesterol or sulfatide levels.

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