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: Mahesh K Kaushik, Kosuke Aritake, Shinya Kamauchi, Osamu Hayaishi, Zhi-Li Huang, Michael Lazarus, Yoshihiro Urade
• Journal: Experimental neurology (Exp Neurol) Vol. 253 Pg. 82-90 (Mar 2014) ISSN: 1090-2430 [Electronic] United States
• PMID: 24333565 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Convulsants
• Lipocalins
• Receptors, Thromboxane A2, Prostaglandin H2
• Tfdp1 protein, mouse
• Transcription Factor DP1
• 6-Ketoprostaglandin F1 alpha
• Intramolecular Oxidoreductases
• prostaglandin R2 D-isomerase
• Dinoprostone
• Pentylenetetrazole

Topics

• 6-Ketoprostaglandin F1 alpha (metabolism)
• Analysis of Variance
• Animals
• Brain (drug effects, metabolism)
• Convulsants (toxicity)
• Dinoprostone (metabolism)
• Disease Models, Animal
• Electroencephalography
• Electromyography
• Intramolecular Oxidoreductases (deficiency, physiology)
• Lipocalins (physiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Pentylenetetrazole (toxicity)
• Receptors, Thromboxane A2, Prostaglandin H2 (metabolism)
• Seizures (chemically induced, genetics, metabolism, physiopathology)
• Sleep, REM (drug effects, genetics, physiology)
• Time Factors
• Transcription Factor DP1 (deficiency)