Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice
Background: Febrile seizures (FSs) are the most frequent type of seizures in infancy and childhood. Epileptiform discharges (EDs) on electroencephalogram at the time of first FS recurrence can increase the risk of epilepsy development. Therefore, inhibition of EDs is important. Recently, WS-3, a tra...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1138673/full |
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| author | Hiroshi Moriyama Sadahiro Nomura Sadahiro Nomura Hirochika Imoto Hirochika Imoto Fumiaki Oka Yuichi Maruta Naomasa Mori Natsumi Fujii Michiyasu Suzuki Hideyuki Ishihara |
| author_facet | Hiroshi Moriyama Sadahiro Nomura Sadahiro Nomura Hirochika Imoto Hirochika Imoto Fumiaki Oka Yuichi Maruta Naomasa Mori Natsumi Fujii Michiyasu Suzuki Hideyuki Ishihara |
| author_sort | Hiroshi Moriyama |
| collection | DOAJ |
| description | Background: Febrile seizures (FSs) are the most frequent type of seizures in infancy and childhood. Epileptiform discharges (EDs) on electroencephalogram at the time of first FS recurrence can increase the risk of epilepsy development. Therefore, inhibition of EDs is important. Recently, WS-3, a transient receptor potential melastatin 8 (TRPM8) agonist, reportedly suppressed penicillin G-induced cortical-focal EDs. However, the effects of TRPM8 agonists on FSs remain unknown. In this study, we aimed to clarify the effects of the TRPM8 agonist, and the absence of TRPM8 channels, on hyperthermia-induced FS by analyzing the fast ripple band.Methods: Hyperthermia (43°C for 30 min) induced by a heating pad caused FSs in postnatal day 7 wild-type (WT) and TRPM8 knockout (TRPM8KO) mice. FSs were defined as EDs occurring during behavioral seizures involving hindlimb clonus and loss of the righting reflex. Mice were injected with 1% dimethyl sulfoxide or 1 mM WS-3 20 min before the onset of hyperthermia, and electroencephalograms; movies; and rectal, brain and heating pad temperatures were recorded.Results: In wild-type mice, WS-3 reduced the fast ripple amplitude in the first FS without changing rectal and brain temperature thresholds. In contrast, the anti-FS effect induced by the TRPM8 agonist was not observed in TRPM8KO mice and, compared with wild-type mice, TRPM8 deficiency lowered the rectal and brain temperature thresholds for FSs, exacerbated the fast ripple amplitude, and prolonged the duration of the initial FS induced by hyperthermia.Conclusion: Our findings suggest that TRPM8 agonists can be used to treat hyperthermia-induced FSs. |
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| language | English |
| last_indexed | 2024-04-10T05:13:42Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-59af360fd85f49acb43b4a91413fbbd12023-03-09T05:38:56ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.11386731138673Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant miceHiroshi Moriyama0Sadahiro Nomura1Sadahiro Nomura2Hirochika Imoto3Hirochika Imoto4Fumiaki Oka5Yuichi Maruta6Naomasa Mori7Natsumi Fujii8Michiyasu Suzuki9Hideyuki Ishihara10Departments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanEpilepsy Center, Yamaguchi University Hospital, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanEpilepsy Center, Yamaguchi University Hospital, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanDepartments of Neurosurgery, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, JapanBackground: Febrile seizures (FSs) are the most frequent type of seizures in infancy and childhood. Epileptiform discharges (EDs) on electroencephalogram at the time of first FS recurrence can increase the risk of epilepsy development. Therefore, inhibition of EDs is important. Recently, WS-3, a transient receptor potential melastatin 8 (TRPM8) agonist, reportedly suppressed penicillin G-induced cortical-focal EDs. However, the effects of TRPM8 agonists on FSs remain unknown. In this study, we aimed to clarify the effects of the TRPM8 agonist, and the absence of TRPM8 channels, on hyperthermia-induced FS by analyzing the fast ripple band.Methods: Hyperthermia (43°C for 30 min) induced by a heating pad caused FSs in postnatal day 7 wild-type (WT) and TRPM8 knockout (TRPM8KO) mice. FSs were defined as EDs occurring during behavioral seizures involving hindlimb clonus and loss of the righting reflex. Mice were injected with 1% dimethyl sulfoxide or 1 mM WS-3 20 min before the onset of hyperthermia, and electroencephalograms; movies; and rectal, brain and heating pad temperatures were recorded.Results: In wild-type mice, WS-3 reduced the fast ripple amplitude in the first FS without changing rectal and brain temperature thresholds. In contrast, the anti-FS effect induced by the TRPM8 agonist was not observed in TRPM8KO mice and, compared with wild-type mice, TRPM8 deficiency lowered the rectal and brain temperature thresholds for FSs, exacerbated the fast ripple amplitude, and prolonged the duration of the initial FS induced by hyperthermia.Conclusion: Our findings suggest that TRPM8 agonists can be used to treat hyperthermia-induced FSs.https://www.frontiersin.org/articles/10.3389/fphar.2023.1138673/fullelectrocorticogramsfast ripplefebrile seizureshyperthermialoss of righting reflextransient receptor potential melastatin 8 (TRPM8) |
| spellingShingle | Hiroshi Moriyama Sadahiro Nomura Sadahiro Nomura Hirochika Imoto Hirochika Imoto Fumiaki Oka Yuichi Maruta Naomasa Mori Natsumi Fujii Michiyasu Suzuki Hideyuki Ishihara Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice Frontiers in Pharmacology electrocorticograms fast ripple febrile seizures hyperthermia loss of righting reflex transient receptor potential melastatin 8 (TRPM8) |
| title | Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice |
| title_full | Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice |
| title_fullStr | Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice |
| title_full_unstemmed | Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice |
| title_short | Suppressive effects of a transient receptor potential melastatin 8 (TRPM8) agonist on hyperthermia-induced febrile seizures in infant mice |
| title_sort | suppressive effects of a transient receptor potential melastatin 8 trpm8 agonist on hyperthermia induced febrile seizures in infant mice |
| topic | electrocorticograms fast ripple febrile seizures hyperthermia loss of righting reflex transient receptor potential melastatin 8 (TRPM8) |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1138673/full |
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