Mol Nutr Food Res. 2022 Sep 13:e2200275. Epub 2022 Sep 13. PMID: 36099650
DHA and EPA Prevent Seizure and Depression-Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode-of-actions in a Pentylenetetrazole-Induced Kindling Model in Mice.
SCOPE: It has been reported that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anticonvulsant effects, yet the respective mechanism of EPA and DHA on epilepsy are still unclarified. This study aimed to investigate the effect of EPA and DHA on pentylenetetrazol (PTZ) induced seizures and depression.METHODS AND RESULTS: The administration of EPA and DHA at a dose of 1% (w/w) significantly inhibited PTZ-induced seizures and depressive-like behavior, whereas EPA outcompetes DHA. Further mechanistic studies revealed that the higher effect of EPA can be partly attributed to the promotion of M2 polarization, inhibition of M1 polarization of microglia, and lower iron content in the brain, resulting from the stronger activation of nuclear factor E2-related factor 2 (Nrf2). We found that DHA and EPA comparably inhibited NLRP3 inflammasome activation but with different mode-of-actions: EPA preferred to inhibit the binding of NLRP3 and ASC, while DHA decreased the protein levels of ASC and Caspase-1.CONCLUSIONS: These results indicated that DHA and EPA could efficaciously alleviate PTZ-induced seizure and depressive-like behavior but with different efficiency and molecular mechanisms. This article is protected by copyright. All rights reserved.