title: Commentary on Kaushik et al.: Prostaglandin D2 is crucial for seizure suppression and postictal sleep. Novel evidence supporting a role for prostanoid receptors in seizure control.
abstract: Accumulating clinical and experimental evidence suggests a role for prostaglandins (PGs) in epilepsy and isolated seizures. Prostaglandin levels are increased in the hippocampus of epileptic patients and in the cerebrospinal fluid of children with febrile seizures. Moreover, increased PGD2, PGE2 and PGF2α levels are found in the brain after chemically-induced seizures and in spontaneously epileptic mice. However, whether prostaglandins facilitate or decrease seizures has been a matter of debate in the literature. Both pro- and anticonvulsant activities have been described for most of prostaglandins, except for PGD2 and DP receptor agonists, for which a consistent anticonvulsant action has been reported. The study by Kaushik and colleagues elegantly extends this view by showing that hematopoietic PGD synthase (H-PGDS) and DP1 receptors are essential for seizure suppression and that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2/DP1 system regulates sleep that follows PTZ-induced seizures using knockout animals. This commentary discusses the experimental approach of the studies that have implicated prostaglandins and their receptors in seizures, the interesting approach and results of Kaushik and colleagues, and the challenges of considering PGD2 signaling as a therapeutic target in epilepsy.
authors.affiliation: Department of Physiology and Pharmacology, Center of Health Sciences, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900 RS, Brazil. Electronic address: cf.mello@smail.ufsm.br.
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: Mello
authors.affiliation: Department of Physiology and Pharmacology, Center of Health Sciences, Universidade Federal de Santa Maria (UFSM), Santa Maria, 97105-900 RS, Brazil.
authors.forename: Mauro Schneider
authors.initials: MS
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology*; D012890:Sleep / Q000187:drug effects*
chemical_list: D000927:Anticonvulsants; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2
keywords: DP(1) receptors; Epilepsy; Inflammation; PGD(2); Prostaglandins; Seizure