Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), 28789 East Jingshi Road, Jinan, 250103, Shandong Province, People's Republic of China.
Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, 28789 East Jingshi Road, Jinan, 250103, Shandong Province, People's Republic of China.
Neurochem Res. 2018 Apr;43(4):904-917. doi: 10.1007/s11064-018-2496-9. Epub 2018 Feb 7.
Pentylenetetrazole (PTZ)-induced seizures in Zebrafish models are now widely accepted for investigating human disease epilepsy. In epilepsy, the generation of oxidative stress contributes to the brain injury. Although Gastrodin (GAS) has been reported to have anticonvulsant activities, its effects on zebrafish seizure models and the underlying mechanism remain unclear. In this study, we evaluated the effects of GAS pretreatment on PTZ-induced seizures in zebrafish larvae and investigated the underlying mechanism related to its anti-oxidative defense. We found for the first time that GAS significantly decreased seizure-like behavior and extended the latency period to the onset of seizures. In addition, after exposure to GAS, anti-oxidative activity was observed in PTZ-induced seizures by measurement of antioxidant enzymes activities and oxidative stress-related genes expression. The overall results indicate that GAS attenuates PTZ-induced seizures in a concentration-dependent manner and modulates oxidative stress to potentially protect larval zebrafish from further seizures. Furthermore, our results have provided novel insights into GAS related therapy of seizures and associated neurological disorders.
戊四氮（PTZ）诱导的斑马鱼癫痫模型现在被广泛用于研究人类疾病癫痫。在癫痫中，氧化应激的产生导致脑损伤。虽然天麻素（GAS）已被报道具有抗惊厥活性，但它对斑马鱼惊厥模型的影响及其潜在机制尚不清楚。在这项研究中，我们评估了 GAS 预处理对斑马鱼幼虫 PTZ 诱导惊厥的影响，并研究了与其抗氧化防御相关的潜在机制。我们首次发现 GAS 可显著减少惊厥样行为，并延长发作前的潜伏期。此外，在 GAS 暴露后，通过测量抗氧化酶活性和氧化应激相关基因表达，观察到 GAS 在 PTZ 诱导的惊厥中具有抗氧化活性。总体结果表明，GAS 以浓度依赖的方式减轻 PTZ 诱导的惊厥，并调节氧化应激，从而潜在地保护幼鱼免受进一步的惊厥。此外，我们的研究结果为 GAS 治疗惊厥和相关神经障碍提供了新的见解。
