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Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model
Cyclooxygenases (COX)-1 and -2 are isoenzymes that catalyze the conversion of arachidonic acid into prostaglandins (PGs). COX-2 and PGs are rapidly increased following seizures and are known to play important roles in the neuroinflammatory process. COX-2 isoform has been predominantly explored as th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108920/ https://www.ncbi.nlm.nih.gov/pubmed/27895618 http://dx.doi.org/10.3389/fneur.2016.00200 |
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author | Barbalho, Patrícia Gonçalves Carvalho, Benilton de Sá Lopes-Cendes, Iscia Maurer-Morelli, Claudia Vianna |
author_facet | Barbalho, Patrícia Gonçalves Carvalho, Benilton de Sá Lopes-Cendes, Iscia Maurer-Morelli, Claudia Vianna |
author_sort | Barbalho, Patrícia Gonçalves |
collection | PubMed |
description | Cyclooxygenases (COX)-1 and -2 are isoenzymes that catalyze the conversion of arachidonic acid into prostaglandins (PGs). COX-2 and PGs are rapidly increased following seizures and are known to play important roles in the neuroinflammatory process. COX-2 isoform has been predominantly explored as the most suitable target for pharmacological intervention in epilepsy studies, while COX-1 remains poorly investigated. In the present study, we evaluated the effects of selective COX-1 inhibitor or selective COX-2 inhibitor on seizure suppression in the zebrafish pentylenetetrazole (PTZ)-seizure model. Zebrafish larvae were incubated in 5 μM of SC-236 for 24 h or 2.8 μM of SC-560 for 30 min, followed by exposure to 15 mM PTZ for 60 min. Real-time quantitative PCR analysis was carried out to investigate transcription levels of cox1 (ptgs1), as well as to determine cfos levels, used as a marker for neuronal activity. Effects of selective COX-2 or COX-1 inhibitors on locomotor activity response (velocity and distance moved) during PTZ exposure were evaluated using the Danio Vision video-tracking system. Our results showed an inducible expression of the cox1 gene after 60 min of PTZ exposure. Cox1 mRNA levels were upregulated compared with the control group. We found that COX-2 inhibition treatment had no effect on zebrafish PTZ-induced seizures. On the other hand, COX-1 inhibition significantly attenuated PTZ-induced increase of locomotor activity and reduced the c-fos mRNA expression. These findings suggest that COX-1 inhibition rather than COX-2 has positive effects on seizure suppression in the zebrafish PTZ-seizure model. |
format | Online Article Text |
id | pubmed-5108920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-51089202016-11-28 Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model Barbalho, Patrícia Gonçalves Carvalho, Benilton de Sá Lopes-Cendes, Iscia Maurer-Morelli, Claudia Vianna Front Neurol Neuroscience Cyclooxygenases (COX)-1 and -2 are isoenzymes that catalyze the conversion of arachidonic acid into prostaglandins (PGs). COX-2 and PGs are rapidly increased following seizures and are known to play important roles in the neuroinflammatory process. COX-2 isoform has been predominantly explored as the most suitable target for pharmacological intervention in epilepsy studies, while COX-1 remains poorly investigated. In the present study, we evaluated the effects of selective COX-1 inhibitor or selective COX-2 inhibitor on seizure suppression in the zebrafish pentylenetetrazole (PTZ)-seizure model. Zebrafish larvae were incubated in 5 μM of SC-236 for 24 h or 2.8 μM of SC-560 for 30 min, followed by exposure to 15 mM PTZ for 60 min. Real-time quantitative PCR analysis was carried out to investigate transcription levels of cox1 (ptgs1), as well as to determine cfos levels, used as a marker for neuronal activity. Effects of selective COX-2 or COX-1 inhibitors on locomotor activity response (velocity and distance moved) during PTZ exposure were evaluated using the Danio Vision video-tracking system. Our results showed an inducible expression of the cox1 gene after 60 min of PTZ exposure. Cox1 mRNA levels were upregulated compared with the control group. We found that COX-2 inhibition treatment had no effect on zebrafish PTZ-induced seizures. On the other hand, COX-1 inhibition significantly attenuated PTZ-induced increase of locomotor activity and reduced the c-fos mRNA expression. These findings suggest that COX-1 inhibition rather than COX-2 has positive effects on seizure suppression in the zebrafish PTZ-seizure model. Frontiers Media S.A. 2016-11-15 /pmc/articles/PMC5108920/ /pubmed/27895618 http://dx.doi.org/10.3389/fneur.2016.00200 Text en Copyright © 2016 Barbalho, Carvalho, Lopes-Cendes and Maurer-Morelli. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Barbalho, Patrícia Gonçalves Carvalho, Benilton de Sá Lopes-Cendes, Iscia Maurer-Morelli, Claudia Vianna Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model |
title | Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model |
title_full | Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model |
title_fullStr | Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model |
title_full_unstemmed | Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model |
title_short | Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model |
title_sort | cyclooxygenase-1 as a potential therapeutic target for seizure suppression: evidences from zebrafish pentylenetetrazole-seizure model |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108920/ https://www.ncbi.nlm.nih.gov/pubmed/27895618 http://dx.doi.org/10.3389/fneur.2016.00200 |
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