Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model.

Abstract

Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3a) shows reduced excitatory neurotransmission but lower seizure threshold. The neural mechanism linking the synaptic dysfunction to the seizure remains elusive. We show that the local circuits of Ube3ain vitro are hyperexcitable and display a unique epileptiform activity, a phenomenon that is reminiscent of the finding in fragile X syndrome (FXS) mouse model. Similar to the FXS model, lovastatin suppressed the epileptiform activity and audiogenic seizures in Ube3a. The in vitro model of Ube3ais valuable for dissection of neural mechanism and epilepsy drug screening in vivo.