Subject Area

Biological Sciences, General, Cell Biology, Life Sciences, Molecular Biology, Neuroscience, Physiology

Abstract

Sudden unexpected death in epilepsy (SUDEP), the primary cause of mortality in epilepsy, remains poorly understood. Studies suggest seizures may trigger dangerous signals affecting the heart and lungs leading to collapse and death. The Kv1.1 deficiency mouse model mirrors clinical SUDEP cases, showing spontaneous seizures, cardiorespiratory issues, and premature death. However, this model lacks regional specificity in Kv1.1 deletion, hindering insights into SUDEP’s mechanisms and anatomical substrates.

This dissertation employs three distinct conditional knockout (cKO) techniques to investigate the individual roles for the forebrain, brainstem, and heart in SUDEP related phenotypes. The findings reveal that the forebrain alone can trigger spontaneous seizures and premature death. Additionally, the brainstem may play a significant role in regulating blood oxygen levels and may show gender differences in respiratory measures. Lastly, Kv1.1 in the heart is essential for cardiomyocyte action potential repolarization but does not significantly impact overall cardiac function measured in mice. This research highlights how distinct brain circuits contribute to SUDEP mechanisms, providing insights specifically for researchers using the Kv1.1 deficiency model as to where the crucial anatomical substrates may be found in future studies.

Degree Date

Spring 2024

Document Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

Advisor

Dr. Edward Glasscock

Number of Pages

144

Format

.pdf

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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