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ZFIN ID: ZDB-PUB-160311-7
Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae
Barbalho, P.G., Lopes-Cendes, I., Maurer-Morelli, C.V.
Date: 2016
Source: BMC Neuroscience 17: 12 (Journal)
Registered Authors:
Keywords: Seizure, Zebrafish, Pentylenetetrazol, Interleukin-1 beta, Cyclooxygenase-2, Indomethacin, Inflammation
MeSH Terms:
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal/administration & dosage*
  • Brain/drug effects
  • Brain/metabolism*
  • Brain/physiopathology*
  • Cyclooxygenase 2/metabolism*
  • Disease Models, Animal
  • Down-Regulation
  • Fish Proteins/metabolism
  • Indomethacin/administration & dosage*
  • Inflammation/metabolism*
  • Inflammation Mediators/metabolism
  • Interleukin-1beta/metabolism*
  • Pentylenetetrazole
  • RNA, Messenger/metabolism
  • Seizures/chemically induced
  • Seizures/metabolism*
  • Zebrafish
PubMed: 26961169 Full text @ BMC Neurosci.
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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 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.
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.
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.
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