Abstract

Epilepsy is a worldwide public health concern associated with debilitating neurological, cognitive, and psychosocial consequences. Current antiepileptic drugs can have debilitating side effects and new treatments are needed for individuals with pharmaco-resistant seizures like those observed in temporal lobe epilepsy (TLE). Ellagic acid (EA), a polyphenol present in several fruits and nuts, has shown beneficial effects in rodent models of epilepsy and anxiety, possibly mediated through GABAergic pathways. Bang-Sensitive Drosophila mutants model epileptic seizures following mechanical shock and provide a high-throughput alternative to costly rodent studies. The objectives of this study were to: 1) examine the effectiveness of seizure modeling in two Bang-Sensitive mutants strains [bang senseless (bss) and easily shocked (eas)], 2) explore the anticonvulsant effects of EA, and 3) investigate EA’s mechanism of action through the addition of two types of GABA antagonists: flumazenil (FL) and picrotoxin (PTX). The results indicated that vortexing consistently induced seizure-like activity (SLA) in both mutant strains. When examining control groups, bss flies exhibited more severe SLA when compared to eas flies. EA slightly reduced SLA in bss flies while both GABA antagonists increased SLA; however these effects were non-significant. Eas flies

receiving EA exhibited significantly less SLA when compared to bss flies. Both GABA antagonists significantly increased SLA in eas flies, with PTX exerting the strongest effect. This possibly indicates that EA’s anticonvulsant effect involves GABAergic systems in a strain-specific manner and may be more likely mediated through a GABAA receptor site than benzodiazepine site. Moreover, utilizing Bang-Sensitive mutants with varying levels of seizure-sensitivity provides a valuable tool for screening plant-based compounds that can be utilized in the treatment of refractory TLE.

LLU Discipline

Clinical Psychology

Department

Clinical Psychology

School

School of Behavioral Health

First Advisor

Hartman, Richard E.

Second Advisor

Fogel, Travis G.

Third Advisor

Haerich, Paul E.

Fourth Advisor

Vermeersch, David A.

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2017

Date (Title Page)

9-2017

Language

English

Library of Congress/MESH Subject Headings

Epilepsy - drug therapy; Anticonvulsants; Epilepsy, Temporal Lobe;

Subject - Local

Polyphenols; Ellagic acid; Bang-Sensitive Drosophila mutants

Type

Dissertation

Page Count

77

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

Share

COinS