THE HIPPOCAMPAL TRANSCRIPTOME AFTER SEIZURE INDUCTION: A COMPARISON OF MODELS

Abstract

Pathogenic mutations in the gene SCN8A, which encodes the sodium channel NaV 1.6, cause generalized seizures as well as intellectual and developmental delays. Seizure onset occurs before 18 months of age, and patients typically respond poorly to most first-line seizure medications. The majority of medications have been and continue to be developed using chemical rodent models that capture seizures caused by severe injury to the brain, primarily in the hippocampus. These injuries result in neuronal death and hippocampal scarring, neither of which have been reported in the literature for SCN8A patients. In this study, the hippocampal transcriptome of SCN8A and kainic acid-treated mice are compared through their differentially expressed genes and biological pathways at various timepoints. The evidence suggests that SCN8A mice see an increase in axonal connections and neuronal signaling, while kainic acidtreated mice do not. This could mean that SCN8A mice experience seizures due to highly interconnected and hyperexcitable neurons, while the kainic acid mice experience seizures due to neurotoxicity. These different mechanisms support the need for new drugs to be tested on both genetic and chemical models if they will be widely prescribed for epilepsy disorders.