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首页> 外文期刊>Experimental Neurology >A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors
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A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors

机译：新型的斑马鱼热疗引起的癫痫发作模型揭示了TRPV4通道和NMDA型谷氨酸受体的作用

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Febrile seizures are the most common seizure type in children under the age of five, but mechanisms underlying seizure generation in vivo remain unclear. Animal models to address this issue primarily focus on immature rodents heated indirectly using a controlled water bath or air blower. Here we describe an in vivo model of hyperthermia-induced seizures in larval zebrafish aged 3 to 7. days post-fertilization (dpf). Bath controlled changes in temperature are rapid and reversible in this model. Acute electrographic seizures following transient hyperthermia showed age-dependence, strain independence, and absence of mortality. Electrographic seizures recorded in the larval zebrafish forebrain were blocked by adding antagonists to the transient receptor potential vanilloid (TRPV4) channel or N-methyl-d-aspartate (NMDA) glutamate receptor to the bathing medium. Application of GABA, GABA re-uptake inhibitors, or TRPV1 antagonist had no effect on hyperthermic seizures. Expression of vanilloid channel and glutamate receptor mRNA was confirmed by quantitative PCR analysis at each developmental stage in larval zebrafish. Taken together, our findings suggest a role of heat-activation of TRPV4 channels and enhanced NMDA receptor-mediated glutamatergic transmission in hyperthermia-induced seizures.
机译：高热惊厥是五岁以下儿童中最常见的惊厥类型，但体内引起惊厥的机制尚不清楚。解决该问题的动物模型主要集中在使用可控水浴或鼓风机间接加热的未成熟啮齿动物上。在这里，我们描述了受精后（dpf）3至7天龄的斑马鱼幼体斑马鱼中高热诱导的癫痫发作的体内模型。在此模型中，浴液控制的温度变化迅速且可逆。短暂性高热后的急性电图惊厥表现出年龄依赖性，菌株依赖性和无死亡率。幼虫斑马鱼前脑中记录的电子癫痫发作可通过向沐浴液中的瞬时受体电位类香草酸（TRPV4）通道或N-甲基-d-天冬氨酸（NMDA）谷氨酸受体添加拮抗剂来阻止。 GABA，GABA再摄取抑制剂或TRPV1拮抗剂的应用对高热惊厥没有影响。通过定量PCR分析在幼虫斑马鱼的每个发育阶段证实了类香草酸通道和谷氨酸受体mRNA的表达。两者合计，我们的研究结果表明热激活TRPV4通道和增强NMDA受体介导的谷氨酸能传递在热疗诱发的癫痫发作中的作用。

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