Talks and posters
Bryan's award winning presentation!
Congratulations Bryan on your award winning presentation!
2nd place in the Student Brain Symposium 2011
Neurophysiological mechanisms in a mouse model of early onset epileptic encephalopathy
Bryan Leaw, Christopher Reid and Steven Petrou
Howard Florey Institute, Parkville, 3010
Dravet syndrome is a severe epileptic encephalopathy, which lies at the most severe end of the Genetic Epilepsy with Febrile Seizure Plus (GEFS+) spectrum. SCN1A mutations are the most common cause of GEFS+ and account for >70% of patients with Dravet syndrome. Recently however, a patient with Dravet syndrome was reported to be homozygous for a mutation in SCN1B, encoding the β1 subunit of sodium channels. To further elucidate the pathogenesis of SCN1B based Dravet syndrome, we investigated a mouse model homozygous for a common GEFS+ SCN1B mutation, C121W. Mice homozygous for this C121W mutation exhibited the seizure susceptibility and abnormal gait of human Dravet patients, and mirrored human patient responses to specific anti-epileptic drugs (AED). This strongly supported the C121W mouse as a model of Dravet syndrome, therefore we performed neuronal analysis with the presence of the C121W mutation. We examined homozygous subicular neurons, which have been suggested to have a role in thermal seizure genesis. These neurons displayed hallmarks of increased excitability, consisting broader APs and a left-shifted input-output relationship. Interestingly, these neurons displayed intrinsically higher membrane input resistance, which could account for this hyperexcitability. We then tested a novel AED, retigabine, which activates potassium channels and thereby would potentially lower membrane resistance back to wild-type levels. Work done in our laboratory then showed that upon application of retigabine, susceptibility to thermal seizures in these mice was strongly suppressed. This highlights the potential of our mouse model in identifying potential AEDs that could target specific human epileptic syndromes.
 Bryan's Sobr presentation.pdf | [ ] | 989 Kb |