Effects of Maternal Docosahexaenoic Acid Intake on Febrile Seizures and Increased Seizure Susceptibility after Febrile Seizures: Study Using Mouse Models and Human Samples

The effects of docosahexaenoic acid (DHA) on seizures and epilepsy remain controversial and appear to depend on the specific context. In this study, we investigated the effects of maternal DHA intake on febrile seizures and post-febrile seizure susceptibility. Mice exposed to DHA during pregnancy showed considerably higher brain DHA and 17β-estradiol (E2) levels than controls, along with a marked delay in the onset of febrile seizures. These effects were abolished by letrozole, an inhibitor of cytochrome P450 family 19 subfamily A, suggesting that the DHA-induced increase in E2 reduces susceptibility to febrile seizures. Maternal DHA intake also suppressed neuroinflammation after febrile seizures and reduced seizure susceptibility later in life following pentylenetetrazol treatment. These protective effects also required E2 synthesis, as they were abolished by letrozole, indicating that the DHA-induced increase in E2 reduces long-term seizure susceptibility even after febrile seizures have occurred. In children with febrile seizures, serum DHA and E2 levels were markedly lower than those in controls. In addition, serum interleukin-1 beta levels were inversely correlated with serum E2 concentrations. Together, DHA can delay febrile seizure onset and attenuate inflammation in an E2-dependent manner. Maternal DHA intake during pregnancy may therefore contribute to healthy brain development in children.