Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model.

Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3am-/p+) 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 Ube3am-/p+in 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 Ube3am-/p+. The in vitro model of Ube3am-/p+ is valuable for dissection of neural mechanism and epilepsy drug screening in vivo.