Date of Award
Doctor of Philosophy (PhD)
Michael J. Decker PhD, RN, RRT, D. ABSM
Shih-Yu Lee PhD, RNC
Toni Whistler, PhD
Andrew Escayg, PhD
Genetic epilepsy with febrile seizures plus (GEFS+) is associated with a wide range of neurological dysfunction caused in part by limited function in voltage-gated sodium channels (Escayg & Goldin, 2010; Gambardella & Marini, 2009; Mulley et al., 2005). The seizure and behavioral phenotypes, as well as use of non-pharmacologic agents as neuroprotectants in GEFS+, are not well-understood. An experimental design used an animal model of GEFS+ to 1. explore the effects of stress on seizure phenotype, 2. examine behavioral phenotypes, and 3. study the effects of an omega 3 fatty acid on abnormal behaviors noted in the various paradigms.
This study used C57BL/6J mice with the R1648H missense mutation on the Scn1a gene (engineered in the Escayg lab) (Martin, M. S. et al., 2010). The three specific aims used separate groups of animals for experimentation, and all paradigms were performed under strict laboratory conditions.
Data were analyzed using either an independent t-tests, two-way ANOVA or repeated measures two-way ANOVA. Results showed that stress worsens seizure phenotype in both the Scn1aR1648H (RH) mutants and wild-type (WT) group with the RH mutants more severely impacted. In addition, there was clear and consistent evidence for hyperactive locomotor behavior. Lastly, no evidence was found for use of docosahexaenoic acid (DHA, an omega 3 fatty acid) as a neuroprotectant for hyperactivity (DHA was given subcutaneously for two weeks starting at weaning).
Outcomes from this study implicate that stress worsens the seizure phenotype in animals with Scn1aR1648H. This study is also the first to report hyperactive locomotor behavior in animals with Scn1aR1648H. Results from this study may broaden beyond GEFS+ in that we may also be able to apply the findings to other disorders with SCN1A dysfunction. In addition, it may be that genetic variants affecting SCN1A, but not necessarily in epilepsy, may contribute to hyperactivity. This could mean that SCN1A is a candidate gene for hyperactivity. The main goal of nursing care is to reduce and prevent disease morbidity, and knowledge gained from the current study will guide clinical nursing practice, such as targeted behavioral assessment and education, as well as nursing research focusing on children with this genetic disorder.
Helvig, Ashley W., "Seizure and Behavioral Phenotyping of the Scn1a Mouse Model of Genetic Epilepsy with Febrile Seizures Plus." Dissertation, Georgia State University, 2012.