Dissertation/Thesis Abstract

The author has requested that access to this graduate work be delayed until 2019-09-13. After this date, this graduate work will be available on an open access basis.
Protecting Synaptic Function from Acute Oxidative Stress: A Novel Role for Big K+ (BK) Channels and Resveratrol-Like Compounds
by Bollinger, Wesley L., Ph.D., Florida Atlantic University, 2018, 137; 10826799
Abstract (Summary)

Oxidative stress causes neural damage and inhibits essential cellular processes, such as synaptic transmission. Despite this knowledge, currently available pharmaceutical agents cannot effectively protect neural cells from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries in a real life clinical setting. Our lab has developed an electrophysiology protocol to identify novel drugs that protect an essential cellular process (neurotransmission) from acute oxidative stress-induced damage. Through this doctoral dissertation, we have identified three new drugs, including a Big K+ (BK) K+ channel blocker (iberiotoxin), resveratrol, and a custom made resveratrol-like compound (fly2) that protect synaptic function from oxidative stress-induced insults. Further developing these drugs as neuroprotective agents may prove transformative in protecting the human brain from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries.

Inhibiting the protein kinase G (PKG) pathway protects neurotransmission from acute oxidative stress. This dissertation has expanded upon these findings by determining that the PKG pathway and BK K+ channels function through independent biochemical pathways to protect neurotransmission from acute oxidative stress. Taken together, this dissertation has identified two classes of compounds that protect neurotransmission from acute oxidative stress, including resveratrol-like compounds (resveratrol, fly2) and a BK K + channel inhibitor (iberiotoxin). Further developing these drugs in clinical trials may finally lead to the development of an effective neuroprotective agent.

Indexing (document details)
Advisor: Dawson-Scully, Kenneth
Commitee: Dawson-Scully, Kenneth, Hughes, Colin, Ja, William, Macleod, Gregory
School: Florida Atlantic University
Department: Biological Sciences
School Location: United States -- Florida
Source: DAI-B 80/02(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Neurosciences
Keywords: BK channels, Hydrogen peroxide, Iberiotoxin, Neuroprotection, Resveratrol, Synaptic transmission
Publication Number: 10826799
ISBN: 9780438447035
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