The Influence Of Recurrent Febrile Seizures To The Brain Function In Scn1a Mutant Rats

IntroductionSCN1A mutations have been examined in febrile seizures, infantile severe myoclonic epilepsy and generalized epilepsy febrile seizures plus etc. SCN1A mutations are linked to GEFS+. Some patients with GEFS+also exhibit anxiety, mental retardation, autistic behavior and ataxia. These complications might be caused by recurrent seizures, modifier genes, or environmental factors. The mechanism has remained unclear. Therefore, in this study, hyperthermia induced seizure susceptibility rats with Scnla missense mutation were used to observe their physiological Motor function, emotion, learning and memory functions, moreover, the influence of recurrent febrile seizures to their brain function.Materials and methodsMale F344/NSlc wild-type rats and F344/NSlc-Scnla mutant rats which have a missense (N1417H) mutation in the voltage gated sodium channel al subunit gene (Scnla) and exhibit clonic seizures induced by hyperthermia were used. The rats were divided into 3 groups:wild-type (G1), Scnla mutant rats with no induction of febrile seizure (G2), and Scnla mutant rats with induction (from 5-week old, every other day, for 5 times) of febrile seizure (G3). For behavioral experiments, footprint gait analysis, balance beam test, elevated plus maze test and 8-arm radial maze test were performed successively with a few days'interval from 12-week old. And for electrophysiological experiment, the rats of the 3 groups were decapitated and their brains were removed to record LTP (long term potentiation) at the age of 7-8 weeks'old. ResultsThere were no significant differences among the 3 groups in footprint gait analysis or elevated plus maze test; but in balance beam test, compared with the wild-type (G1), mutant rats with no FS (febrile seizure) (G2) and mutant rats with FS (G3) showed significantly increased foot slips, and in radial maze test, rats of G2 and G3 made significantly more total errors and reference memory errors than those of group 1. At the same time the results of electrophysiological experiment were in consistent with the results above. Rats in G2 and G3 exhibited significantly lower LTP level than those in G1. However, there were no significant differences found between G2 and G3 in any of these experiments.ConclusionAll the results indicate that F344/NSlc-Scnla mutant rats display a complication of ataxia and memory dysfunction, what's more, though febrile seizure was induced 5 times in G3, the symptoms are not worse than those mutant rats with no induction of febrile seizure.