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Seizure is one of the most frequent neurological emergencies among neonates. Seizures during neurodevelopment could promote epileptogenesis by triggering inflammatory cascades and potentiating mTOR signaling. Epileptogenesis contemplates disrupted neurogenesis and neurodegeneration; and culminates in epilepsy. Epileptic patients suffer from unpredictable and recurrent seizures, which lead to social, psychological, and cognitive impairment. In this context, developing efficient treatments to manage neonatal seizures is compulsory. Here, we aimed to investigate the antiseizure and neuroprotective potential of luteolin and micronized luteolin in zebrafish larvae at 5 days post-fertilization. Both luteolin and micronized luteolin reduced the occurrence of each seizure stage and slowed the seizure development. Furthermore, there were no residual effects on larvae motor function 24 hours after the pentylenetetrazole-induced seizures. Finally, the expression level of genes related to the inflammatory response (interleukin-1β, interleukin-6, and TNF-α), mTOR signaling (p70S6Ka and p70S6Kb), neurogenesis (BDNF), and apoptosis (caspase-3) were not altered 24 hours after the seizure occurrence. In conclusion, our study demonstrates for the first time that luteolin and micronized luteolin present antiseizure effects in developing zebrafish. The data encourage further investigations looking to new approaches to neonatal seizure management.

The increase in proinflammatory cytokine expression causes behavioral changes consistent with sickness behavior, and this led to the suggestion that depression might be a psychoneuroimmunological phenomenon. Here, we evaluated the effects of the pretreatment with fluoxetine (10 mg/kg, i.p.) and curcumin (0.5 mg/kg, i.p.) on the immune response elicited by the inoculation of an Aeromonas hydrophila bacterin in zebrafish. Nonpretreated but A. hydrophila-inoculated and sham-inoculated groups of fish served as controls. The social preference, locomotor, exploratory activities, and cerebral expression of il1b, il6, tnfa, and bdnf mRNA were compared among the groups. Behavioral changes characteristic of sickness behavior and a significant increase in the expression of il1b and il6 cytokines were found in fish from the immunostimulated group. The behavioral alterations caused by the inflammatory process were different between males and females, which was coincident with the increased expression of cerebral BDNF. Fluoxetine and curcumin prevented the sickness behavior induced by A. hydrophila and the increased expression of proinflammatory cytokines. Our results point to the potential of zebrafish as a translational model in studies related to neuroinflammation and demonstrate for the first time the effects of fluoxetine and curcumin on zebrafish sickness behavior.