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Roles of prostaglandins D_2 and E_2 in the site of action for their sleep-wake regulation

前列腺素 D_2 和 E_2 在睡眠-觉醒调节作用部位的作用

基本信息

批准号：
06454709
负责人：
MATSUMURA Hitoshi
金额：
$ 4.16万
依托单位：
Osaka Bioscience Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454709/
关键词：
Prostaglandin D_2 Sleep Rostral basal forebrain A_2-adenosine receptor Cerebrospinal fluid Accumbens nucleus Olfactory tubercle Prostaglandin D synthase 覚醒対角帯イボテン酸脳血流アデノシン NO

项目摘要

The site of action for the sleep-promoting effect of prostaglandin (PG) D_2 had been postulated to be located in the preoptic area, a sleep center ; however, our experimental results showed that the real site of action is located in the ventral surface of a basal-forebrain region located rostral to the preoptic area. This basal-forebrain region includes ventral striatum, i.e., the accumbens nucleus and the olfactory tubercle, as well as the diagonal band of Broca and the septal region. We also demonstrated that changes in the regional blood flow in this area are closely correlated with the changes in the sleep-wake state. The brain PGD synthase, the enzyme responsible for the synthesis of PGD_2 in the brain, was shown to be abundantly expressed in the leptomeninges covering the surface of the brain. The concentration of PGD_2 in the cerebrospinal fluid (CSF) of the rat was higher during the daytime, the sleeping period of the animal, than during the night. Thus, it is postulated that PGD_2 synthesized in the membrane tissues surrounding the ventral surface of the rostral basal forebrain acts at the surface layr of the brain region to initiate sleep. The signal produced by PGD_2 may be transmitted to neural circuits responsible for the sleep-wake regulation. In the process, A_<2a>-adenosine receptors abundantly expressed in the ventral striatum are crucially involved, because CGS21680, an A_<2a>-adenosine agonist, markedly promoted sleep when administered to the same region, whereas KF17837, an A_2-adenosine antagonist, inhibited the sleep promotion produced by PGD_2. The region including the ventral striatum may serve as an interface structure between, humoral and neuronal mechanisms for the sleep-wake regulation.

前列腺素(PG)D_2促进睡眠的作用部位被认为位于视前区，即睡眠中枢；然而，我们的实验结果表明，真正的作用部位位于位于视前区吻侧的基底-前脑区的腹面。这个基底-前脑区域包括腹侧纹状体，即伏隔核和嗅结节，以及Broca斜带和隔区。我们还证明了该区域血流的变化与睡眠-觉醒状态的变化密切相关。脑PGD合成酶是脑内合成PGD_2的酶，在覆盖大脑表面的软脑膜中大量表达。大鼠脑脊液中前列腺素D_2的浓度在白天动物睡眠期间高于夜间。因此，推测前脑吻侧腹侧表面膜组织合成的PGD_2作用于脑区表层，启动睡眠。PGD_2产生的信号可能被传递到负责睡眠-觉醒调节的神经回路。在这个过程中，在腹侧纹状体大量表达的腺苷受体是至关重要的，因为在同一区域给药时，腺苷激动剂CGS21680显著促进睡眠，而A2-腺苷拮抗剂KF17837抑制PGD_2产生的睡眠促进作用。包括腹侧纹状体在内的区域可能是调节睡眠觉醒的体液和神经机制之间的接口结构。