Characterization of Seizure Induction Methods in Drosophila.
Characterization of Seizure Induction Methods in Drosophila.
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DOI：
10.1523/eneuro.0079-21.2021
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发表时间：
2021-07-01
期刊：
影响因子：
3.4
通讯作者：
Baines, Richard A
中科院分区：
文献类型：
--
作者：
Mituzaite, Jurga;Petersen, Rasmus;Baines, Richard A
癫痫是最常见的神经系统疾病之一。大约三分之一的患者对目前的药物没有反应。这种缺乏治疗表明需要更好地了解潜在的机制，重要的是，需要确定药物操作的新靶点。果蝇（Drosophila melanogaster）具有快速的繁殖时间、强大的遗传学特性，并有利于大样本量，使其成为癫痫发作机制的强大模型。为了更好地了解主要苍蝇发作基因型的行为和生理表型，我们系统地测量了幼虫和成虫阶段的发作严重程度和次级行为表型。几种癫痫诱导方法的比较，特别是电，机械和热诱导，表明幼虫电击是最有效的诱导癫痫发作在广泛的癫痫倾向突变体测试。成年和幼虫的运动被认为是癫痫易感性的非预测。在确定的幼虫运动神经元的记录活动揭示了动作电位（AP）模式的变化，在不同的基因型，但这些模式并没有与癫痫发作的易感性。综上所述，虽然在机械诱导、热诱导和次级表型方面存在很大差异，但电击是果蝇中已知的主要癫痫发作基因型中最一致的癫痫发作诱导方法。
Epilepsy is one of the most common neurologic disorders. Around one third of patients do not respond to current medications. This lack of treatment indicates a need for better understanding of the underlying mechanisms and, importantly, the identification of novel targets for drug manipulation. The fruit fly Drosophila melanogaster has a fast reproduction time, powerful genetics, and facilitates large sample sizes, making it a strong model of seizure mechanisms. To better understand behavioral and physiological phenotypes across major fly seizure genotypes we systematically measured seizure severity and secondary behavioral phenotypes at both the larval and adult stage. Comparison of several seizure-induction methods; specifically electrical, mechanical and heat induction, show that larval electroshock is the most effective at inducing seizures across a wide range of seizure-prone mutants tested. Locomotion in adults and larvae was found to be non-predictive of seizure susceptibility. Recording activity in identified larval motor neurons revealed variations in action potential (AP) patterns, across different genotypes, but these patterns did not correlate with seizure susceptibility. To conclude, while there is wide variation in mechanical induction, heat induction, and secondary phenotypes, electroshock is the most consistent method of seizure induction across known major seizure genotypes in Drosophila.