Frequency of Each Sex Affected by Sudden Unexplained Deaths due to Developmental Epilepsy

Developmental epilepsy is a group of neurodevelopmental disorders that is mainly characterized by the onset of different types of seizures, developmental delays, and electroencephalogram (EEG) changes at a young age. Because it can describe a variety of syndromes, symptoms and specific causes may vary between affected individuals. Previous research has examined sex differences within affected adult populations but research examining sex differences for developmental epilepsy is lacking. The objective of this research is to determine the frequency of each sex within a population of mice that died prematurely from developmental epilepsy due to mutations of the GABAA receptor α2 subunit. To determine the frequency of each sex, we extracted DNA from the tails of pups that died prematurely. We determined their sex by running PCR to amplify the sex-determining region on the Y chromosome (SRY). PCR products were separated by agarose gel electrophoresis. Males are identified by the presence of two bands of 300 and 350 base pairs (bp) while females are identified by one single band of 350 bp. Current research provides evidence that males are at higher risk for sudden unexplained death in epilepsy (SUDEP). The current study aims to examine whether males are at higher risk in our model of developmental epilepsy. Future research can provide additional insight into the mechanisms that lead to differences in SUDEP risk.https://digitalscholarship.unlv.edu/durep_posters/1038/thumbnail.jp

Morphology of Axon Initial Segments under Normal and Pathological Conditions

The Axon Initial Segment (AIS) is a compartment within the neuron that plays a major role in the initiation of action potentials. Changes to AIS length and position can alter the probability of action potential firing. A majority of modeling studies consider the AIS to have linear morphology; however, we have observed different AIS shapes in different pathological conditions. The objective of this research is to classify AISs by shape (straight, curved, or kinked) and to determine the frequency of each shape across normal and pathological conditions. We stained AISs in cortical tissue using immunohistochemistry and imaged them with a confocal microscope. After imaging, we qualitatively categorized AISs in normal and pathological samples based on their shape and plotted them in ImageJ to obtain numerical data (Cartesian coordinates). We have compared AISs in cortical tissue from wild type mice to those from the Mecp2+/- model of Rett syndrome. We plan to use the Cartesian data to develop a model that describes the linear and non-linear morphologies of the AIS. Although previous research has demonstrated that position, composition, and length of AISs helps determine neuronal excitability, the relationship between AIS shape and pathology has not been examined. The current study helps establish AIS morphology as a possible pathological feature that may have functional consequences, and future experiments will investigate a relationship between AIS shape and neuronal excitability. Additional research may help to gain a deeper understanding of normal and pathological development and may lead to the development of new treatments.https://digitalscholarship.unlv.edu/durep_posters/1039/thumbnail.jp