Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Neuroscience

First Advisor

Stewart A. Anderson

Abstract

Epilepsy is a neurological seizure disorder affecting approximately 1% of the world’s population. Seizure disorders are numerous, heterogeneous, and can develop from a multitude of physiological conditions including but not limited to interneuron dysfunction, ion channel mutations, irregular development and layering of the cerebral cortex, abnormalities in cell signaling pathways, brain tumors, traumatic brain injuries, and mitochondrial diseases. In many seizure disorders, gene mutations (primary) cause physiological abnormalities (secondary) that result in seizures. In some cases, the primary cause of epilepsy remains unknown, and in other cases, the secondary cause remains to be determined. My thesis research identified a novel, exogenous primary contributor to epilepsy in a specific subtype of cortical malformation disorders, as well as a secondary astrocytic irregularity resulting from a mitochondria-related nuclear gene mutation that may contribute to epilepsy. In Chapter 1, I briefly introduce the relationship between cortical malformation disorders, mitochondrial disease, and epilepsy. In Chapter 2, I present data supporting the idea that the cortical dyslamination and resultant epilepsy in focal cortical dysplasia type IIB is caused by the human papillomavirus oncoprotein E6. In Chapter 3, I present data on astrocyte-specific irregularities resulting from mitochondrial aspartate glutamate carrier loss of function and its effects on glutamatergic neurotransmission, and speculate on the role and importance of astrocytes in seizure genesis and propagation.

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