Indomethacin Treatment Prior To Pentylenetetrazole-induced Seizures Downregulates The Expression Of Il1b And Cox2 And Decreases Seizure-like Behavior In Zebrafish Larvae

dc.creatorBarbalho
dc.creatorPG; Lopes-Cendes
dc.creatorI; Maurer-Morelli
dc.creatorCV
dc.date2016
dc.date2016-12-06T18:31:31Z
dc.date2016-12-06T18:31:31Z
dc.date.accessioned2018-03-29T02:04:09Z
dc.date.available2018-03-29T02:04:09Z
dc.identifier
dc.identifierBmc Neuroscience. BIOMED CENTRAL LTD, n. 17, n. 12, p. .
dc.identifier1471-2202
dc.identifierWOS:000371974400001
dc.identifier10.1186/s12868-016-0246-y
dc.identifierhttp://bmcneurosci.biomedcentral.com.ez88.periodicos.capes.gov.br/articles/10.1186/s12868-016-0246-y
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/320315
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1311081
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionIt 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.
dc.description17
dc.description
dc.description
dc.description
dc.descriptionBrazilian Institute of Neuroscience and Neuro-technology BRAINN-CEPID [2013/07559-3]
dc.descriptionFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2014/15640-8, 2013/19151-9]
dc.descriptionConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [475405/2010-2]
dc.descriptionFAPESP
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description
dc.description
dc.description
dc.languageEnglish
dc.publisherBIOMED CENTRAL LTD
dc.publisherLONDON
dc.relationBMC Neuroscience
dc.rightsaberto
dc.sourceWOS
dc.subjectSeizure
dc.subjectZebrafish
dc.subjectPentylenetetrazol
dc.subjectInterleukin-1 Beta
dc.subjectCyclooxygenase-2
dc.subjectIndomethacin
dc.subjectInflammation
dc.titleIndomethacin Treatment Prior To Pentylenetetrazole-induced Seizures Downregulates The Expression Of Il1b And Cox2 And Decreases Seizure-like Behavior In Zebrafish Larvae
dc.typeArtículos de revistas


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