洛伐他汀抑制 Angelman 综合征模型中的过度兴奋和癫痫发作。
Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model.
机构信息
Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, United States.
Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, United States.
出版信息
Neurobiol Dis. 2018 Feb;110:12-19. doi: 10.1016/j.nbd.2017.10.016. Epub 2017 Oct 31.
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 Ube3a is valuable for dissection of neural mechanism and epilepsy drug screening in vivo.
摘要
癫痫在 Angelman 综合征（AS）中很常见，且通常难以用医学方法治疗。AS 小鼠模型（Ube3a）表现出兴奋性神经递质传递减少，但癫痫发作阈值降低。将突触功能障碍与癫痫发作联系起来的神经机制仍不清楚。我们发现 Ube3a 的体外局部回路过度兴奋，并表现出独特的癫痫样活动，这一现象让人联想到脆性 X 综合征（FXS）小鼠模型的发现。与 FXS 模型类似，洛伐他汀抑制了 Ube3a 的癫痫样活动和听觉性癫痫发作。Ube3a 的体外模型对于神经机制的剖析和体内抗癫痫药物的筛选都很有价值。
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