Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

NEUROBIOLOGY OF DISEASE

卷:110

Article

Chung, Leeyup^1,5  Bey, Alexandra L.²  Towers, Aaron J.³  Cao, Xinyu¹  Kim, Il Hwan⁴  Jiang, Yong-hui^1,2,3 

[1] Duke Univ, Sch Med, Dept Pediat, Durham, NC 27710 USA

[2] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA

[3] Duke Univ, Sch Med, Univ Program Genet & Genom, Durham, NC 27710 USA

[4] Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA

[5] Korea Brain Res Inst, 61 Cheomdan Ro, Daegu 41068, South Korea

关键词: Angelman syndrome;    Ube3a;    Seizure;    Lovastatin;    Long burst;   

DOI  :  10.1016/j.nbd.2017.10.016

来源: Elsevier

【 摘 要 】

Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3a(m - /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 Ube3a(m - /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 Ube3a(m - /P +). The in vitro model of Ube3a(m - /P +) is valuable for dissection of neural mechanism and epilepsy drug screening in vivo.

【 授权许可】

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