{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:08:07Z","timestamp":1773022087997,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Sudden unexpected death in epilepsy (SUDEP) is a fatal event that ranks second in years of potential life lost among neurological disorders. Seizure-induced respiratory arrest (S-IRA) is the primary instigator leading to death in many SUDEP cases. However, there are currently no effective preventive strategies against S-IRA other than the seizure control. Therefore, it is critical to develop new avenues to prevent SUDEP by investigating the pharmacological interventions of S-IRA. In the present study, we examined the effect of genistein, an isoflavone found in various dietary vegetables, on the incidence of S-IRA in DBA\/1 mice.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> DBA\/1 mice exhibited generalized seizures and S-IRA when subjected to acoustic stimulation. Genistein was intraperitoneally administered alone or in combination with an adrenoceptor antagonist and a serotonin (5-HT) receptor antagonist, respectively. The effects of drug treatments on S-IRA incidence and seizure behaviors were examined.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The incidence of S-IRA in DBA\/1 mice was significantly reduced 2 h after injection of genistein at 1\u201390 mg\/kg as compared with that in the vehicle control. Genistein could block S-IRA without interfering with any component of seizures, especially at relatively lower dosages. The S-IRA-suppressing effect of genistein was reversed by an \u03b12 adrenoceptor antagonist but was not altered by an \u03b11 antagonist. The inhibitory effect of genistein on S-IRA was not affected by a 5-HT<jats:sub>3<\/jats:sub> or 5-HT<jats:sub>2A<\/jats:sub> receptor antagonist.<\/jats:p><jats:p><jats:bold>Significance:<\/jats:bold> Our data show that genistein reduces S-IRA incidence and can specifically block S-IRA in DBA\/1 mice. Its suppressing effect on S-IRA is dependent on activating \u03b12 adrenoceptors. Our study suggests that genistein, a dietary supplement, is potentially useful to prevent SUDEP in at-risk patients.<\/jats:p>","DOI":"10.3389\/fneur.2021.761912","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T06:26:15Z","timestamp":1636007175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA\/1 Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Jialing","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Min","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-Jun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1111\/epi.12666","article-title":"Sudden unexpected death in epilepsy: assessing the public health burden","volume":"55","author":"Thurman","year":"2014","journal-title":"Epilepsia."},{"key":"B2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/epi.13234","article-title":"Who to target in sudden unexpected death in epilepsy prevention and how? 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