The Effects of Seizure Modeling and Polyphenols on Behavior in Bang-Sensitive Drosophila

<p>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 </p> <p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Clinical Psychology

Year

2017

Author dc:creator

• Smith, Alphonso A.

Contributors dc:contributor

• Hartman, Richard E.
• Fogel, Travis G.
• Haerich, Paul E.
• Vermeersch, David A.

• Clinical Psychology
• Psychology
• Social and Behavioral Sciences
• Epilepsy - drug therapy; Anticonvulsants; Epilepsy; Temporal Lobe;
• Polyphenols; Ellagic acid; Bang-Sensitive Drosophila mutants

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/430

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1425