Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression: Evidences from Zebrafish Pentylenetetrazole-Seizure Model

• Published in: Frontiers in neurology Vol. 7; p. 200
• Main Authors: Barbalho, Patrícia Gonçalves, Carvalho, Benilton de Sá, Lopes-Cendes, Iscia, Maurer-Morelli, Claudia Vianna
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 15.11.2016
• Subjects: anticonvulsant; cyclooxygensases; Neuroinflammation; Neuroscience; Seizures; Zebrafish model; zebrafish model; seizures; anticonvulsant; neuroinflammation; cyclooxygenases
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2016.00200

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 ( ), as well as to determine 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 gene after 60 min of PTZ exposure. 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 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.