Honors Theses

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Date of Award

2023

Document Type

Honors Thesis - NSU Access Only

Department

College of Psychology

Honors College

Farquhar Honors College

Honors College Dean

Andrea Nevins, Ph.D.

Home College Dean

Karen Grosby, Ed.D.

Faculty Advisor

Lisa Robison, Ph.D.

Abstract

Consumption of a high fat diet contributes to metabolic disease (e.g. obesity and Type 2 diabetes), as well as several neurological disorders. Our previous work has shown that a high fat diet results in sex-specific effects in C57Bl/6J mice, including adult hippocampal neurogenesis, neuroinflammation, and performance on cognitive-behavioral tasks. In general, females are more negatively impacted compared to males, even when the metabolic effects of high fat diet are similar amongst the sexes. The ketogenic diet is a popular fad diet that involves consumption of limited carbohydrates ( < 5%), moderate protein intake, and very high fat. Limiting the intake of carbohydrates induces a state of “nutritional ketosis” that promotes ketogenesis while reducing gluconeogenesis. This causes ketone bodies to replace glucose as the body’s primary energy source. While the ketogenic diet is also very high in fat content, it appears to hold potential for neuroprotection against brain aging and neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease), as well as boost mood and cognitive function in young healthy individuals. Further research on the effects of the ketogenic diet remains to be underexplored in a sex-specific manner as the underlying mechanisms are poorly understood. Additionally, most prior research using animal models have generally used a very strict ketogenic diet that is not ideal for translational relevance (nearly 0% carbohydrates). Therefore, the goal of this study is to compare the effects of both a high fat and translationally relevant ketogenic diet to a low-fat control diet on metabolic outcomes and hippocampal neurogenesis in adult male and female mice. Male HFD mice experienced decreased cell proliferation while female HFD mice experienced decreased neuroblasts. Female keto mice seem to be unaffected in terms of markers for neurogenesis while male keto mice displayed decreased cell proliferation, yet an increased number of neuroblasts. This suggests that the ketogenic diet should have no effect on women, but further studies are required to determine its safety in men.

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