An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior.

An Scn1a epilepsy mutation in Scn8a alters seizure susceptibility and behavior.
Exp Neurol. 2015 Sep 24;
Authors: Makinson CD, Dutt K, Lin F, Papale LA, Shankar A, Barela AJ, Liu R, Goldin AL, Escayg A
Abstract
Understanding the role of SCN8A in epilepsy and behavior is critical in light of recently identified human SCN8A epilepsy mutations. We have previously demonstrated that Scn8a(med) and Scn8a(med-jo) mice carrying mutations in the Scn8a gene display increased resistance to flurothyl and kainic acid-induced seizures; however, they also exhibit spontaneous absence seizures. To further investigate the relationship between altered SCN8A function and epilepsy, we introduced the SCN1A-R1648H mutation, identified in a family with generalized epilepsy with febrile seizures plus (GEFS+), into the corresponding position (R1627H) of the mouse Scn8a gene. Heterozygous R1627H mice exhibited increased resistance to some forms of pharmacologically and electrically induced seizures and the mutant Scn8a allele ameliorated the phenotype of Scn1a-R1648H mutants. Hippocampal slices from heterozygous R1627H mice displayed decreased bursting behavior compared to wild-type littermates. Paradoxically, at the homozygous level, R1627H mice did not display increased seizure resistance and were susceptible to audiogenic seizures. We furthermore observed increased hippocampal pyramidal cell excitability in heterozygous and homozygous Scn8a-R1627H mutants, ...

Source: Experimental Neurology - September 24, 2015 Category: Neurology Authors: Makinson CD, Dutt K, Lin F, Papale LA, Shankar A, Barela AJ, Liu R, Goldin AL, Escayg A Tags: Exp Neurol Source Type: research