Prostaglandin D2 is crucial for seizure suppression and postictal sleep
Prostaglandin D2 is crucial for seizure suppression and postictal sleep
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DOI：
10.1016/j.expneurol.2013.12.002
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发表时间：
2014-03-01
影响因子：
5.3
通讯作者：
Urade, Yoshihiro
中科院分区：
文献类型：
--
作者：
Kaushik, Mahesh K.;Aritake, Kosuke;Urade, Yoshihiro
癫痫是一种伴有癫痫发作的神经系统疾病，通常伴有睡眠。前列腺素(PG)D-2由造血型或脂钙素型前列腺素D合成酶(H-或L-PGDS)产生，参与生理睡眠的调节。在这里，我们发现H-PGDS、L/H-PGDS或DP1R受体(DP1R)KO小鼠表现出更强烈的戊四氮(PTZ)诱导的癫痫发作的潜伏期、全身强直-阵挛发作的持续时间和癫痫发作尖峰的数量。癫痫发作显著增加野生型小鼠脑内PGD(2)含量。这种PTZ诱导的PGD(2)增加在L或H-PGDS KO小鼠的脑中被减弱，而在L/H-PGDS KO小鼠中被取消。在野生型、H-PGDS或DP2RKO小鼠中观察到非快动眼睡眠，而在L、L/H-PGDS或DP1RKO小鼠中未观察到。这些结果表明，由H-PGDS产生的作用于DP1R的PGD(2)对癫痫的抑制是必不可少的，L-PGDS/PGD(2)/DP1R系统调节癫痫发作后的睡眠。(C)2013 Elsevier Inc.保留所有权利。
Epilepsy is a neurological disorder with the occurrence of seizures, which are often accompanied by sleep. Prostaglandin (PG) D-2 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 PGD(2) content of the brain in wild-type mice. This PTZ-induced increase in PGD(2) 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 PGD(2) produced by H-PGDS and acting on DP1R is essential for seizure suppression and that the L-PGDS/PGD(2)/DP1R system regulates sleep that follows seizures. (C) 2013 Elsevier Inc. All rights reserved.