Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/320315
Type: Artigo de Periódico
Title: Indomethacin Treatment Prior To Pentylenetetrazole-induced Seizures Downregulates The Expression Of Il1b And Cox2 And Decreases Seizure-like Behavior In Zebrafish Larvae
Author: Barbalho
PG; Lopes-Cendes
I; Maurer-Morelli
CV
Abstract: It 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 inter-leukin-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. Results: We 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. Conclusions: This 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.
Subject: Seizure
Zebrafish
Pentylenetetrazol
Interleukin-1 Beta
Cyclooxygenase-2
Indomethacin
Inflammation
Editor: BIOMED CENTRAL LTD
Rights: aberto
Identifier DOI: 10.1186/s12868-016-0246-y
Address: http://bmcneurosci.biomedcentral.com.ez88.periodicos.capes.gov.br/articles/10.1186/s12868-016-0246-y
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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