title: Prostaglandin D(2) is crucial for seizure suppression and postictal sleep.
abstract: Epilepsy is a neurological disorder with the occurrence of seizures, which are often accompanied by sleep. Prostaglandin (PG) D2 is produced by hematopoietic or lipocalin-type PGD synthase (H- or L-PGDS) and involved in the regulation of physiological sleep. Here, we show that H-PGDS, L/H-PGDS or DP1 receptor (DP1R) KO mice exhibited more intense pentylenetetrazole (PTZ)-induced seizures in terms of latency of seizure onset, duration of generalized tonic-clonic seizures, and number of seizure spikes. Seizures significantly increased the PGD2 content of the brain in wild-type mice. This PTZ-induced increase in PGD2 was attenuated in the brains of L- or H-PGDS KO and abolished in L/H-PGDS KO mice. Postictal non-rapid eye movement sleep was observed in the wild-type and H-PGDS or DP2R KO, but not in the L-, L/H-PGDS or DP1R KO, mice. These findings demonstrate that PGD2 produced by H-PGDS and acting on DP1R is essential for seizure suppression and that the L-PGDS/PGD2/DP1R system regulates sleep that follows seizures.
authors: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
authors: Mahesh K
authors: MK
authors: Kaushik
authors: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
authors: Kosuke
authors: K
authors: Aritake
authors: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
authors: Shinya
authors: S
authors: Kamauchi
authors: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
authors: Osamu
authors: O
authors: Hayaishi
authors: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan; Department of Pharmacology, Fudan University Shanghai Medical College, 138 Yixueyuan Road, Shanghai 200032, China.
authors: Zhi-Li
authors: ZL
authors: Huang
authors: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan. Electronic address: lazarus.michael.ka@u.tsukuba.ac.jp.
authors: Michael
authors: M
authors: Lazarus
authors: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan. Electronic address: urade.yoshihiro.ft@u.tsukuba.ac.jp.
authors: Yoshihiro
authors: Y
authors: Urade
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000502:physiology*; D054834:Lipocalins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010433:Pentylenetetrazole / Q000633:toxicity; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D012895:Sleep, REM / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D050680:Transcription Factor DP1 / Q000172:deficiency
chemical_list: D003292:Convulsants; D054834:Lipocalins; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C493736:Tfdp1 protein, mouse; D050680:Transcription Factor DP1; D015121:6-Ketoprostaglandin F1 alpha; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015232:Dinoprostone; D010433:Pentylenetetrazole
keywords: CRTH2 (DP(2)) receptor; Convulsion; Electrographic seizures; Postictal EEG depression; Prostaglandin E(2); Prostaglandin F(2)α; Prostanoid; REM sleep