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Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish

机译：雷帕霉素在斑马鱼的不同发育阶段抑制PTZ诱导的癫痫发作

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The mTORC1 complex integrates different inputs from intracellular and extracellular signals to control various cellular processes. Therefore, any disruption in the mTORC1 pathway could promote different neurological disorders. mTORC1 overactivation has been verified in different genetic and acquired epilepsy animal models. Therefore, inhibitors of this complex could have both antiepileptogenic and antiseizure effects. In our study, we investigated the effects of rapamycin pretreatment on pentylenetetrazole (PTZ)-induced seizures in zebrafish. Our results have shown that the latency to reach the tonic-clonic stage (stage III) of progressive behavioral alterations shown during PTZ-induced seizures was prolonged in larval (7 days post fertilization, 7 dpf), juvenile (45 days post fertilization, 45 dpf) and adult (6-8 months) zebrafish after pretreatment with rapamycin. Furthermore, rapamycin pretreatment did not alter the locomotor activity in zebrafish. Therefore, the results obtained in our study indicate that rapamycin pretreatment is an important mechanism to control the progress of seizures in zebrafish throughout different developmental stages (larval, juvenile, and adult). Taken as a whole, our data support that rapamycin has immediate antiseizure effects and could be a potential alternative therapy for seizure control in epilepsy. (C) 2015 Elsevier Inc. All rights reserved.
机译：MTORC1复合物从细胞内和细胞外信号集成不同的输入，以控制各种细胞过程。因此，MTORC1途径中的任何破坏可以促进不同的神经系统疾病。 MTORC1过活化已经在不同的遗传和获得的癫痫动物模型中核实。因此，这种复合物的抑制剂可以具有抗癫痫发育和抗性肿瘤作用。在我们的研究中，我们调查了雷帕霉素预处理对斑马鱼中五苯甲酸四唑（PTZ）诱导的癫痫发作的影响。我们的研究结果表明，在PTZ诱导的癫痫发作期间逐渐显示的渐进性行为改变的滋补卷曲阶段（第III阶段III）在幼虫（施肥后7天，7DPF后7天，施肥后45天，45 DPF）和成人（6-8个月）用雷帕霉素预处理后斑马鱼。此外，雷帕霉素预处理没有改变斑马鱼的运动活性。因此，我们研究中获得的结果表明雷帕霉素预处理是控制在不同发育阶段（幼虫，幼年和成人）的斑马鱼中癫痫发作进展的重要机制。作为一个整体，我们的数据支持雷帕霉素具有即时抗肿瘤效果，并且可能是癫痫癫痫发作控制的潜在替代疗法。 （c）2015 Elsevier Inc.保留所有权利。

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