INTRODUCTION Epilepsy is one of the main clinical problems in Angelman syndrome (AS). Seizures typically start in early childhood then decrease or are often alleviated by young adulthood. Several studies using AS model mice showed comparable seizure susceptibility during young adulthood. In contrast, the course of epilepsy post young adulthood differs from persistently relieved to rerising among reports. To elucidate this, we evaluated the seizure susceptibility of AS model mice of two different ages. METHODS Mice lacking maternal Ube3a gene (Ube3am-/p+) of C57BL/6 background or their littermate wild type (WT) were divided into two groups by age, 2 to 3 months (2-3 M) and 6 to 12 months (6-12 M), corresponding to adolescent to young adult aged and middle aged humans, respectively. Seizure susceptibility was evaluated by flurothyl inhalation or intraperitoneal injection of pentylenetetrazole (PTZ IP)-induced acute seizure protocol. RESULTS In the flurothyl-induced seizure paradigm, the latency to seizure occurrence had a significant interaction with genotype and age. Post-hoc analysis revealed that the latency was significantly shorter at 6-12 M than at 2-3 M in Ube3am-/p+ mice, and in Ube3am-/p+ mice than in WT mice at 6-12 M. No significant interaction or difference was observed by PTZ IP. CONCLUSION The flurothyl-induced seizure paradigm revealed that seizure susceptibility of Ube3am-/p+ mice increased with age, similar to clinical studies reporting the reappearance of epilepsy in older age. The flurothyl-induced seizure paradigm applied to middle-aged Ube3am-/p+ mice could be a suitable protocol for screening drugs against seizures in AS.

中文翻译：

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Flurothyl 诱导的癫痫范例显示中年 Angelman 综合征小鼠模型中更高的癫痫易感性

引言 癫痫是 Angelman 综合征 (AS) 的主要临床问题之一。癫痫发作通常在儿童早期开始，然后减少或通常在成年后缓解。几项使用 AS 模型小鼠的研究表明，在年轻的成年期，癫痫发作的易感性相当。相比之下，成年后癫痫病程在报告中从持续缓解到复发不同。为了阐明这一点，我们评估了两个不同年龄的 AS 模型小鼠的癫痫发作易感性。方法 将缺乏 C57BL/6 背景的母体 Ube3a 基因 (Ube3am-/p+) 或其同窝野生型 (WT) 的小鼠按年龄分为 2 至 3 个月 (2-3 M) 和 6 至 12 个月 (6 -12 M)，分别对应于青少年到年轻成人和中年人。通过氟噻唑吸入或腹膜内注射戊四唑 (PTZ IP) 诱导的急性癫痫发作方案来评估癫痫发作的易感性。结果在flurothyl诱导的癫痫范例中，癫痫发作的潜伏期与基因型和年龄有显着的相互作用。事后分析显示，Ube3am-/p+ 小鼠的 6-12 M 潜伏期明显短于 2-3 M，Ube3am-/p+ 小鼠的潜伏期显着短于 6-12 M 的 WT 小鼠。没有显着的相互作用或通过 PTZ IP 观察到差异。结论flurothyl 诱导的癫痫范例表明，Ube3am-/p+ 小鼠的癫痫易感性随着年龄的增长而增加，类似于报告癫痫在老年时再次出现的临床研究。