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

Autor(es)

Barbalho, Patricia Goncalves ^[1] ; Lopes-Cendes, Iscia ^[2] ; Maurer-Morelli, Claudia Vianna ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Sch Med Sci, Dept Med Genet, Lab Zebrafish, 126 Cidade Univ Zeferino Vaz, BR-13083887 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Sch Med Sci, Dept Med Genet, Mol Genet Lab, 126 Cidade Univ Zeferino Vaz, BR-13083887 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC NEUROSCIENCE; v. 17, MAR 9 2016.
• Citações Web of Science: 6

Resumo

Background: 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. (AU)

• Processo FAPESP: 13/19151-9 - Diferentes abordagens terapêuticas para a supressão da crise epiléptica utilizando o modelo animal zebrafish
• Beneficiário: Patrícia Gonçalves Barbalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/07559-3 - Instituto Brasileiro de Neurociência e Neurotecnologia - BRAINN
• Beneficiário: Fernando Cendes
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/15640-8 - Estudos funcionais de genes de inflamação e microRNAs relacionados às crises epilépticas no modelo do zebrafish
• Beneficiário: Cláudia Vianna Maurer Morelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular