Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae

BMC Neuroscience

Research Article

Iscia Lopes-Cendes¹  Claudia Vianna Maurer-Morelli²  Patrícia Gonçalves Barbalho² 

[1] Laboratory of Molecular Genetics, Department of Medical Genetics - School of Medical Sciences, University of Campinas (UNICAMP), Tessália Vieira de Camargo, 126 Cidade Universitaria “Zeferino Vaz”, 13083-887, Campinas, SP, Brazil;Laboratory of Zebrafish, Department of Medical Genetics - School of Medical Sciences, University of Campinas (UNICAMP), Tessália Vieira de Camargo, 126 Cidade Universitaria “Zeferino Vaz”, 13083-887, Campinas, SP, Brazil;

关键词: Seizure;    Zebrafish;    Pentylenetetrazol;    Interleukin-1 beta;    Cyclooxygenase-2;    Indomethacin;    Inflammation;   

DOI  :  10.1186/s12868-016-0246-y

 received in 2015-02-08, accepted in 2015-08-26,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIt has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors.ResultsWe found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased.ConclusionsThis is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results are supported by previous evidences suggesting that zebrafish is a suitable alternative for studying inflammation, seizures, and the effect of anti-inflammatory compounds on seizure suppression.

【 授权许可】

CC BY   
© Barbalho et al. 2016