A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors.
A novel zebrafish model of hyperthermia-induced seizures reveals a role for TRPV4 channels and NMDA-type glutamate receptors.
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DOI：
10.1016/j.expneurol.2012.06.013
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发表时间：
2012-09
影响因子：
5.3
通讯作者：
Baraban SC
中科院分区：
文献类型：
--
作者：
Hunt RF;Hortopan GA;Gillespie A;Baraban SC
热性惊厥是五岁以下儿童最常见的惊厥类型，但体内发生惊厥的机制尚不清楚。解决这一问题的动物模型主要集中在未成熟的啮齿动物身上，这些啮齿动物使用受控水浴或鼓风机间接加热。在这里，我们描述了一种在受精后3至7天（dpf）幼体斑马鱼中高温诱发癫痫发作的体内模型。在这个模型中，浴槽控制的温度变化是快速和可逆的。短暂性热疗后的急性电痉挛表现出年龄依赖性、应变独立性和无死亡率。在洗液中加入瞬时受体电位香草素（TRPV4）通道或n -甲基-d-天冬氨酸（NMDA）谷氨酸受体拮抗剂，可阻断斑马鱼幼体前脑的电图癫痫发作。应用GABA、GABA再摄取抑制剂或TRPV1拮抗剂对高热发作无影响。定量PCR分析证实了斑马鱼幼鱼各发育阶段香草素通道和谷氨酸受体mRNA的表达。综上所述，我们的研究结果表明TRPV4通道的热激活和NMDA受体介导的谷氨酸能传递在高温诱发癫痫发作中的作用。
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.
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影响因子：
5.3
作者：
Bhaskaran, Muthu D.;Smith, Bret N.
通讯作者：
Smith, Bret N.
DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
影响因子：
82.9
作者：
Chen, K;Baram, TZ;Soltesz, I
通讯作者：
Soltesz, I
影响因子：
5.3
作者：
Brewster, A;Bender, RA;Baram, TZ
通讯作者：
Baram, TZ
DOI：
10.1001/archpedi.1997.02170410045006
发表时间：
1997-04-01
影响因子：
--
作者：
Berg, AT;Shinnar, S;Hauser, AW
通讯作者：
Hauser, AW