Honors Theses

Date of Award

2023

Document Type

Honors Thesis

Degree Type

Bachelors of Science

Degree Name

Neuroscience

Department

College of Psychology

Honors College

Farquhar Honors College Thesis

Honors College Dean

Andrea Nevins, Ph.D., M.F.A.

Home College Dean

Karen Grosby, Ed.D.

Faculty Advisor

Lisa Robison, Ph.D.

Abstract

Poor diet and metabolic diseases (obesity, Type 2 diabetes) are associated with increased risk of neurodegenerative and neuropsychiatric disorders, including Alzheimer’s disease, anxiety, and depression. Studies indicate that inflammation in the hippocampus could be one mechanism linking these conditions. Previous findings on inflammation, specifically glial activity in response to a high-fat diet, indicate sex differences in microglial responses in the hippocampus. The ketogenic diet is characterized by a high-fat, low-carbohydrate, and moderate-protein diet. While the ketogenic diet is very high in fat content, it may also possess neuroprotective properties against brain aging and neurodegenerative disorders, as well as boost mood and cognitive function. The aim of the experiment is to examine further the sex-specific effects of a high-fat diet (HFD) and a translationally relevant ketogenic diet (KD) on inflammation in the hippocampus, with a specific focus on astrocytes. Male and female C57BL/6J mice were fed high-fat, ketogenic, or low-fat control diets starting at 9 weeks of age and remained on the diet for ~5 months. Mice were assessed for weight gain, adiposity, ketone body levels, and diabetic status using glucose tolerance testing. Immunofluorescence was performed using a GFAP antibody for the analysis of astrocytes in the hippocampus. In males, there was no effect of diet on GFAP labeling in any subregion of the hippocampus. However, in female KD mice, there was a decrease in GFAP percent area covered in the CA1 and CA2 regions of the hippocampus, with similar but non-significant trends in other hippocampus regions (CA3 and dentate gyrus). These findings suggest that KD affects hippocampal astrocytes in a sex-specific manner, though further research is necessary to evaluate the downstream and functional effects of these changes.

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