Electrophysiological and pharmacological characterization of spreading depolarization in the adult zebrafish tectum
Electrophysiological and pharmacological characterization of spreading depolarization in the adult zebrafish tectum
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DOI：
10.1152/jn.00343.2021
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发表时间：
2021-12-01
影响因子：
2.5
通讯作者：
Aizawa, Hidenori
中科院分区：
文献类型：
--
作者：
Terai, Haruhi;Gwedela, Mayeso Naomi Victoria;Aizawa, Hidenori
扩散性去极化(SD)是一种缓慢传播的神经元和神经胶质细胞去极化波。越来越多的研究表明，SD和SD样现象在偏头痛、中风和创伤性脑损伤等神经疾病中发挥作用。尽管SD具有重要的临床意义，但其潜在的分子和细胞机制仍然难以捉摸，可能是因为没有足够的动物模型来进行基因操作。这样的模型还将允许对抑制SD的药物开发进行高通量筛选。为了解决这个问题，我们开发了一种新的实验系统来研究斑马鱼的SD。在固定的成年斑马鱼的电生理记录中发现，细胞外钾浓度的增加引起SD，视顶盖直流电(DC)电位出现较大且持续的负移。降低细胞外场电位的振荡活性，增加即刻早期基因c-fos的表达。药物阻断N-甲基-D-天冬氨酸(NMDA)谷氨酸受体可抑制SD的增殖，提示谷氨酸能神经传递介导斑马鱼顶盖SD。我们的分析表明，斑马鱼的顶盖和啮齿动物的皮质具有相似的SD动力学。目前的研究为斑马鱼SD和哺乳动物SD具有可比性提供了电生理和药理学证据。该斑马鱼SD模型适用于遗传操作和高性价比的高通量筛选。这可能为适用于SD相关神经疾病的新的诊断和治疗方法铺平道路。新的和值得注意的先前研究涉及中风和偏头痛的扩散性去极化(SD)。在这里，我们第一次展示了SD，在成年斑马鱼的顶盖中，表现出波形动力学，c-fos的表达，以及在啮齿动物皮质中观察到的N-甲基-D-天冬氨酸谷氨酸受体阻滞剂的减弱。由于斑马鱼是一种可以进行遗传操作和化学筛选的动物模型，这一结果可能为适用于SD相关神经疾病的新诊断和治疗方法铺平道路。
Spreading depolarization (SD) is a slowly propagating wave of neuronal and glial depolarization. A growing number of studies show that SD and SD-like phenomena play a role in neurological disorders such as migraine, stroke, and traumatic brain injury. Despite the clinical importance of SD, its underlying molecular and cellular mechanisms remain elusive, possibly because of insufficient animal model allowing genetic manipulation. Such a model would also allow high-throughput screening for SD-suppressing drug development. To address this, we developed a novel experimental system to study SD using zebrafish. Electrophysiological recordings in the immobilized adult zebrafish revealed that increasing extracellular potassium concentration elicited SD with a large and long-lasting negative shift of direct current (DC) potential in the optic tectum. It also reduced the oscillatory activity in the extracellular field potential and increased the expression of the immediate early gene c-fos. Pharmacological blocking of the N-methyl-D-aspartate (NMDA) glutamate receptor attenuated the propagation of SD, suggesting that glutamatergic neurotransmission mediated tectal SD in zebrafish. Our analyses revealed that the zebrafish tectum and rodent cortex had similar SD kinetics. The current study provides electrophysiological and pharmacological evidence that zebrafish SD and mammal SD are comparable. This zebrafish SD model is suitable for genetic manipulation and cost-effective high-throughput screening. It could pave the way to novel diagnostic and therapeutic methods applicable to SD-associated neurological disorders.NEW & NOTEWORTHY Previous studies have implicated spreading depolarization (SD) in stroke and migraine. Here, we demonstrate SD, for the first time, in the adult zebrafish tectum showing waveform kinetics, c-fos expression, and attenuation by Nmethyl-D-aspartate glutamate receptor blocker as observed in the rodent cortex. Since the zebrafish is an animal model amenable to genetic manipulation and chemical screening, this result could pave the way to novel diagnostic and therapeutic methods applicable to SD-associated neurological disorders.