权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neural circuit for the sleep-wake regulation by prostaglandins D_2 and E_2

前列腺素 D_2 和 E_2 调节睡眠-觉醒的神经回路

基本信息

批准号：
04404026
负责人：
HAYAISHI Osamu
金额：
$ 17.92万
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 (A)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

项目摘要

We previously hypothesized that prostaglandin (PG) D_2 and PGE_2 are endogenous sleep-wake regulating substances. In this study, we examined the site of action of the sleep-promoting effect of PGD_2 with more than 200 rats and found that continuous and bilateral infusion of PGD_2 into the subarachnoid space under the rostal basal forebrain increased slow-wave sleep up to the maximum level that can be attained physiologically. This PGD_2-sensitive, sleep-promoting zone spreads beneath the horizontal limb of the diagonal band and even towards rostral under the basal forebrain. Thus, the site of action was confined in the ventral region of the rostral basal forebrain. Our group also demonstrated that the brain type PGD synthase, which is the major enzyme responsible for the synthesis of PGD_2 in the brain, is crucial for the maintenance of physiological sleep : i.e., administration of inhibitors of this enzyme caused total insomnia. By use of in situ hybridization and immunohistochemical staining, it was shown that this enzyme is mainly located in the choroid plexus, leptomeninges, and, in less degree, the white matter. It was also demonstrated that the cerebrospinal fluid (CSF) exhibited PGD synthase activity with a highest specific activity among various brain tissues examined. The second most abundant protein in the CSF,which was known as beta-trace, was shown to be identical to the PGD synthase itself. Based on the results of this reserach, it is hypothesized that PGD_2 synthesized in the surface layr of the brain acts as a sleep promoter at the ventral surface zone of the rostral basal forebrain, and that the PGD_2 and PGD synthase (or beta-trace) in the CSF also play important roles in the sleep-wake regulation.

我们先前假设前列腺素D_2和前列腺素E_2是内源性睡眠-觉醒调节物质。在本研究中，我们用200多只大鼠观察了PGD_2促进睡眠的作用部位，发现将PGD_2持续和双侧注入基底前脑吻侧下蛛网膜下腔可使慢波睡眠增加，达到生理上所能达到的最大水平。这个对PGD2敏感的促进睡眠的区域分布在斜角带水平支的下方，甚至延伸到基底前脑下方的吻部。因此，作用部位被限制在吻侧基底前脑的腹侧区域。我们的研究小组还证明，脑型PGD合成酶是大脑中合成PGD_2的主要酶，对维持生理睡眠至关重要：即服用该酶的抑制剂会导致完全失眠。通过原位杂交和免疫组织化学染色，发现该酶主要定位于脉络丛、软脑膜，少量分布于脑白质。脑脊液具有PGD合酶活性，是各种脑组织中比活性最高的。脑脊液中第二丰富的蛋白质，被称为β-TRACE，被证明与PGD合成酶本身相同。根据本研究结果，推测脑表层合成的PGD_2在基底前脑吻侧腹侧表面区起睡眠促进剂的作用，脑脊液中的PGD_2和PGD合成酶(或β-TRACE)在睡眠-觉醒调节中也起重要作用。