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Forebrain glutamate uptake and behavioral parameters are altered in adult zebrafish after the induction of Status Epilepticus by kainic acid
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-04-19
Ben Hur Marins Mussulini, Adriana Fernanda Kuckartz Vizuete, Marcos Braga, Luana Moro, Suelen Baggio, Emerson Santos, Gabriela Lazzarotto, Kamila Cagliari Zenki, Letícia Pettenuzzo, João Batista Texeira Rocha, Diogo Losch de Oliveira, Maria Elisa Calcagnotto, José Angelo Silveira Zuanazzi, Javier Santos Burgos, Eduardo Pacheco Rico

The development of new antiepileptic drugs is a high-risk/high-cost research field, which is made even riskier if the behavioral epileptic seizure profile is the unique approach on which the development is based. In order to increase the effectiveness of the screening conducted in the zebrafish model of status epilepticus (SE), the evaluation of neurochemical markers of SE would be of great relevance. Epilepsy is associated with changes in the glutamatergic system, and glutamate uptake is one of the critical parameters of this process. In this study therefore, we evaluated the levels of glutamate uptake in the zebrafish brain and analyzed its correlation with the progression of behavioral changes in zebrafish at different times after the administration of kainic acid 5 mg/kg). The results showed that the zebrafish suffered with lethargy while swimming for up to 72 h after SE, had reduced levels of GFAP cells 12 h after SE, reduced levels of S100B up to 72 h after SE, and reduced levels of glutamate uptake in the forebrain between 3 h and 12 h after SE. The forebrain region of adult zebrafish after SE is similar to the neurochemical limbic alterations that are seen in rodent models of SE. This study demonstrated that there is a time window in which to use the KA zebrafish model of SE to explore some of the known neurochemical alterations that have been observed in rodent models of epilepsy and epileptic human patients.



中文翻译:

海藻酸诱导癫痫持续状态后成年斑马鱼的前脑谷氨酸摄取和行为参数发生改变

新的抗癫痫药的开发是一个高风险/高成本的研究领域,如果行为癫痫发作的概况是该开发所基于的独特方法,则其将变得更加危险。为了增加在斑马鱼模型进行筛选的有效性癫痫持续状态SE),神经化学标记物的评估SE将具有重大意义。癫痫与谷氨酸能系统的变化有关,谷氨酸的摄取是该过程的关键参数之一。因此,在这项研究中,我们评估了斑马鱼大脑中谷氨酸的摄取水平,并分析了其与5 mg / kg海藻酸施用后不同时间斑马鱼行为变化进展的相关性。结果表明,与嗜睡遭受的斑马鱼在游泳长达72小时后SE,此前后水平降低GFAP的细胞的12小时SE后,减压S100B的水平高达72小时SE前脑,和降低的谷氨酸摄取的水平SE后3到12小时内。成年斑马鱼的前脑区SE类似于见于啮齿动物模型的神经化学物质的改变边缘SE。这项研究表明,存在一个使用SE的KA斑马鱼模型探索在癫痫和癫痫人类患者的啮齿动物模型中观察到的某些已知神经化学变化的时间窗。

更新日期:2018-04-25
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