Urade Yoshihiro, Mohri Ikuko
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita.
No To Hattatsu. 2006 Sep;38(5):331-3.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) catalyzes the isomerization of PGH2, a common precursor of various prostanoids, to produce PGD2, a potent endogenous somnogen. L-PGDS is localized in the leptomeninges, choroid plexus, and oligodendrocytes of the central nervous system. PGD2 is proposed to be a major humoral sleep-inducing factor accumulated in the brain during wakefulness. PGD2 stimulates DP, receptors localized in the basal forebrain and increases the local extracellular concentration of adenosine, which activates A2A receptor-possessing neurons in the basal forebrain and/or ventrolateral preoptic area (VLPO). The intracerebroventricular infusion of PGD2 or adenosine A2A receptor-agonists induces non-REM sleep and increases the expression of fos protein in VLPO. The activation of VLPO neurons is associated with decreased fos expression in the histaminergic tuberomammillary nucleus (TMN), one of the arousal centers. The GABAergic inhibition of TMN is involved in non-REM sleep induction by PGD2 or adenosine A2A receptor-agonists. The neural network between VLPO and TMN is considered to play a key role in the regulation of vigilance states.
脂联素型前列腺素（PG）D合成酶（L-PGDS）催化各种前列腺素的共同前体PGH2异构化，生成强效内源性促眠剂PGD2。L-PGDS定位于中枢神经系统的软脑膜、脉络丛和少突胶质细胞。PGD2被认为是清醒时在大脑中积累的主要体液性促眠因子。PGD2刺激位于基底前脑的DP受体，并增加局部细胞外腺苷浓度，腺苷激活基底前脑和/或腹外侧视前区（VLPO）中具有A2A受体的神经元。脑室内注入PGD2或腺苷A2A受体激动剂可诱导非快速眼动睡眠，并增加VLPO中fos蛋白的表达。VLPO神经元的激活与觉醒中枢之一的组胺能结节乳头核（TMN）中fos表达降低有关。TMN的GABA能抑制参与了PGD2或腺苷A2A受体激动剂诱导的非快速眼动睡眠。VLPO和TMN之间的神经网络被认为在警觉状态的调节中起关键作用。
