Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice
Objective: 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...
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| Format: | Article |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2021.761912/full |
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| author | Jialing Guo Jialing Guo Jialing Guo Daniel Min Hua-Jun Feng Hua-Jun Feng |
| author_facet | Jialing Guo Jialing Guo Jialing Guo Daniel Min Hua-Jun Feng Hua-Jun Feng |
| author_sort | Jialing Guo |
| collection | DOAJ |
| description | Objective: 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.Methods: 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.Results: The incidence of S-IRA in DBA/1 mice was significantly reduced 2 h after injection of genistein at 1–90 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 α2 adrenoceptor antagonist but was not altered by an α1 antagonist. The inhibitory effect of genistein on S-IRA was not affected by a 5-HT3 or 5-HT2A receptor antagonist.Significance: 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 α2 adrenoceptors. Our study suggests that genistein, a dietary supplement, is potentially useful to prevent SUDEP in at-risk patients. |
| first_indexed | 2024-12-17T23:18:05Z |
| format | Article |
| id | doaj.art-f68c4d05376a47c7a2cf6c876f46fe42 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-17T23:18:05Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-f68c4d05376a47c7a2cf6c876f46fe422022-12-21T21:28:58ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-11-011210.3389/fneur.2021.761912761912Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 MiceJialing Guo0Jialing Guo1Jialing Guo2Daniel Min3Hua-Jun Feng4Hua-Jun Feng5Department of Neurology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Anesthesia, Harvard Medical School, Boston, MA, United StatesDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United StatesDepartment of Anesthesia, Harvard Medical School, Boston, MA, United StatesObjective: 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.Methods: 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.Results: The incidence of S-IRA in DBA/1 mice was significantly reduced 2 h after injection of genistein at 1–90 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 α2 adrenoceptor antagonist but was not altered by an α1 antagonist. The inhibitory effect of genistein on S-IRA was not affected by a 5-HT3 or 5-HT2A receptor antagonist.Significance: 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 α2 adrenoceptors. Our study suggests that genistein, a dietary supplement, is potentially useful to prevent SUDEP in at-risk patients.https://www.frontiersin.org/articles/10.3389/fneur.2021.761912/fullSUDEPS-IRAdietary supplementnorepinephrineserotonintherapeutics |
| spellingShingle | Jialing Guo Jialing Guo Jialing Guo Daniel Min Hua-Jun Feng Hua-Jun Feng Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice Frontiers in Neurology SUDEP S-IRA dietary supplement norepinephrine serotonin therapeutics |
| title | Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice |
| title_full | Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice |
| title_fullStr | Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice |
| title_full_unstemmed | Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice |
| title_short | Genistein, a Natural Isoflavone, Alleviates Seizure-Induced Respiratory Arrest in DBA/1 Mice |
| title_sort | genistein a natural isoflavone alleviates seizure induced respiratory arrest in dba 1 mice |
| topic | SUDEP S-IRA dietary supplement norepinephrine serotonin therapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2021.761912/full |
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