Prostaglandin D2 is crucial for seizure suppression and postictal sleep

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.