title: Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model.
abstract: 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 ofcox1(ptgs1), as well as to determinecfoslevels, 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 thecox1gene after 60 min of PTZ exposure.Cox1mRNA 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 thec-fosmRNA expression. These findings suggest that COX-1 inhibition rather than COX-2 has positive effects on seizure suppression in the zebrafish PTZ-seizure model.
authors.affiliation: Department of Medical Genetics, School of Medical Sciences, University of Campinas , Sao Paulo , Brazil.
authors.forename: Patrícia Gonçalves
authors.initials: PG
authors.lastname: Barbalho
authors.affiliation: Department of Statistics, Institute of Mathematics, Statistics and Scientific Computing, University of Campinas , Sao Paulo , Brazil.
authors.forename: Benilton de Sá
authors.initials: BS
authors.lastname: Carvalho
authors.affiliation: Department of Medical Genetics, School of Medical Sciences, University of Campinas , Sao Paulo , Brazil.
authors.forename: Iscia
authors.initials: I
authors.lastname: Lopes-Cendes
authors.affiliation: Department of Medical Genetics, School of Medical Sciences, University of Campinas , Sao Paulo , Brazil.
authors.forename: Claudia Vianna
authors.initials: CV
authors.lastname: Maurer-Morelli
keywords: anticonvulsant; cyclooxygenases; neuroinflammation; seizures; zebrafish model