Defense Date

2022

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

Dr. Gretchen Neigh McCandless

Second Advisor

Dr. Melissa McGinn

Third Advisor

Dr. Jennifer Wolstenholme

Abstract

Since the 1970s, fructose consumption has dramatically increased within the United States, as well as the world. While adolescents tend to be the largest consumer of fructose, mostly seen in the form of sugary beverages, the consequences of a high fructose diet started in adulthood can also have severe implications on physiological parameters as well as cognition. Several studies have linked fructose consumption to metabolic syndrome, a clustering of symptoms related to overall health, with particular emphasis placed on obesity, type II diabetes, and the relationship with Alzheimer’s Disease. These findings largely stem from the outcomes of studies on cognition, both in humans and rats, assessing the extent to which fructose consumption alters cognitive flexibility. Aging alone is a factor in cognitive decline, yet the extent to which age interacts with diet is largely unknown. Additionally, more emphasis has been placed on uncovering the relationship between diet and mitochondrial respiration as a possible explanation for sex-specific and age-related differences seen in relation to metabolic stress. Mitochondria are particularly vulnerable to metabolic disturbances, and as such, synaptosomal mitochondria in the hippocampus and prefrontal cortex were analyzed in this study. Surmountable evidence can conclude the effects of a fructose-rich diet on the cognition, behavior, and mitochondrial respiration of male rats, yet females are often neglected from studies. Males and females are equally susceptible to the deleterious effects of fructose, but the manifestation of these outcomes differ significantly between the sexes, according to research from our group. Several theories illuminate estrogen as a neuroprotective hormone that allows females to resist the deleterious effects on cognition, which can explain the negative implications of a high fructose diet being displayed in post-menopausal women only. However, females do seem to be more susceptible to physiological perturbations, and as such remains a point of interest. I therefore determined the extent to which a high fructose diet (55% fructose – 55FD) and a medium fructose diet (18% fructose – 18FD) differentially impacted the physiological parameters, cognition, and mitochondrial respiration of 12-month-old (aged) female rats. Additionally, I examined the potential of estrogen as a neuroprotective factor by administering a high fructose diet to ovariectomized and non-ovariectomized 6-month-old female rats. In the first experimental group, the 18FD group showed significantly higher body weights than their counterparts, while amount consumed and caloric efficiency was not significantly distinct. Additionally, all diet groups showed cognitive rigidity, and the 18FD group displayed increased levels of OCR in the hippocampus. In the second experimental group, there were no implications that estrogen/estradiol played a significant role in protecting non-ovariectomized females from the deleterious effects of a high fructose diet.

In this thesis, I will outline current literature on fructose, how it is metabolized, and the associated outcomes of consuming fructose-rich diets. In addition, I describe the experimental set-up and the assessments performed in order to demonstrate the effects of fructose on physiological, cognitive, and mitochondrial function in female Wistar rats. I then describe the results and finally discuss the interpretation of these results as well as highlight potential future directions for this research. This thesis should aid in further illuminating the consequences of consuming fructose in adult females, the extent to which cognition and associated diseases are affected by mitochondrial dysfunction, and the role estrogen plays in sheltering this effect.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-11-2022

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