Lucey Brendan P, Leahy Averi, Rosas Regine, Shaw Paul J
Department of Neurology, Washington University School of Medicine, Saint Louis, MO.
Department of Anatomy and Neurobiology, Washington University School of Medicine, Saint Louis, MO.
Sleep. 2015 May 1;38(5):777-85. doi: 10.5665/sleep.4674.
A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation.
Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB(9ed4)), and in an adult temperature sensitive seizure mutant seizure (sei(ts1)) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB(9ed4) flies was also assessed.
Laboratory.
Drosophila melanogaster.
Sleep deprivation.
Sleep deprivation increased seizure susceptibility in adult sesB(9ed4)/+ and sei(ts1) mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB(9ed4)/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB(9ed4)/+ became adults.
These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity.
睡眠与癫痫发作之间的关系在人类和啮齿动物模型中均有详细描述;然而,这种关系背后的机制尚不清楚。利用具有癫痫发作表型的黑腹果蝇突变体,我们证明癫痫发作活动可因睡眠剥夺而改变。
在成年对敲击敏感的癫痫突变体应激敏感B(sesB(9ed4))以及成年温度敏感癫痫突变体癫痫(sei(ts1))中,于基线状态及12小时睡眠剥夺后评估癫痫发作活动。还评估了睡眠剥夺对年轻、未成熟的sesB(9ed4)果蝇的长期影响。
实验室。
黑腹果蝇。
睡眠剥夺。
睡眠剥夺增加了成年sesB(9ed4)/+和sei(ts1)突变体果蝇的癫痫易感性。当使用RNA干扰破坏sesB时,睡眠剥夺也增加了癫痫易感性。当给sesB(9ed4)/+果蝇服用抗癫痫药物丙戊酸时,睡眠剥夺对癫痫发作活动的影响减弱。与成年果蝇不同,在果蝇早期发育期间进行睡眠剥夺,会导致sesB(9ed4)/+成年后出现慢性癫痫易感性。
这些发现表明果蝇是研究睡眠与癫痫发作活动之间关系的模式生物。