DOI

10.17077/etd.5l60-x98x

Document Type

Dissertation

Date of Degree

Fall 2018

Degree Name

PhD (Doctor of Philosophy)

Degree In

Genetics

First Advisor

Kitamoto, Toshihiro

First Committee Member

Johnson, Wayne

Second Committee Member

Kirby, John

Third Committee Member

Benson, Christopher

Fourth Committee Member

Wu, Chun-Fang

Abstract

Neurological disorders, such as epilepsy, often result from inherited or newly acquired genetic mutations. However, individuals possessing the exact same disease-causing mutations can exhibit dramatic differences in the severity of their symptoms. These differences can be explained in part by environmental factors, such as the microbes in our gut, that play an important role in the manifestation of disease symptoms. Within the last decade, microbes living in the gut have established themselves as an environmental factor with profound effects on our health and well-being. Of special interest is the relationship between the gut microbiota and neurological disease. The goal of my thesis was to: 1) characterize the gut microbiota composition and 2) understand how the gut microbiota modulates seizure-like behavior using Shudderer, a fruit fly (Drosophila melanogaster) model of epilepsy. Shudderer flies possess a mutation in the voltage-gated sodium channel gene and display seizure-like behavioral abnormalities including spontaneous tremors and heat-induced seizures. We identified differences in the microbial composition of the gut microbiota between Shudderer and control (healthy) flies. We also found that by removing the gut microbiota we could improve seizure-like behavior of Shudderer flies as well as another Drosophila mutant harboring a similar genetic mutation. Together, these findings provide evidence that a bidirectional interaction exists between the gut microbiota and neurological function. Since the molecular and cellular mechanisms controlling basic biological processes are highly conserved between fruit flies and humans, these findings are expected to be applicable to mammalian systems, including humans, and may lead to the future development of novel therapeutics to treat epilepsy and other neurological disorders.

Keywords

antioxidant system, Drosophila, microbiota, seizure, voltage-gated sodium channel

Pages

xii, 104 pages

Bibliography

Includes bibliographical references (pages 90-104).

Copyright

Copyright © 2018 Patrick Arthur Lansdon

Included in

Genetics Commons

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