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Invention of brain Wchanisms responsible for the regulation of sleep-wakefulness (consciousness) and consideration of interrelationship between animal studies and clinical cases of sleep-wakefulness disorder

发明负责调节睡眠-觉醒（意识）的大脑机制，并考虑动物研究与睡眠-觉醒障碍临床病例之间的相互关系

基本信息

批准号：
12670963
负责人：
MATSUMURA Hitoshi
金额：
$ 2.05万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

It was found in rats that prostaglandin (PG) E_2 acting in a region of rostral basal forebrain promotes slow wave sleep via activation of EP_4 receptors whereas it increases paradoxical sleep (PS; or rapid eye movement sleep: REM sleep) via activation of EP_2 and EP_4 receptors.We found previously that a nitric oxide (NO) donor compound administered directly to the rat brain decreased PS whereas an NO synthase (NOS) inhibitor increased PS, and that the site of action of these effects was located in an area including midline nuclei of thalamus, lateral hypothalamic area and rostral part of the posterior hypothalamus or in a part of this area. It was shown by use of c-Fos immunohistochemistry in the present project that neurons of thalamic and hypothalamic nuclei such as paraventricular thalamic nucleus - anterior part, paraventricular hypothalamic nucleus - posterior part periventricular hypothalamic nucleus, and suprachiasmatic nucleus are involved in the PS changes caused by the NO donor compound and the NOS inhibitor.We also showed in rats a circadian fluctuation of brain hypocretin-1 (orexin A), which attracts considerable attention as a, narcolepsy-related substance. A member of this project Watanabe succeeded in extracting and identifying a novel PGE synthase, which was found to exist also in the mammalian brains.In clinical investigations directed by Kuroda and Emura, many cases of sleep-wakefulness disorder have been studied. It is expected that pathophysiology underlying sleep-wakefulness disorders and various cases of deteriorated consciousness and art of living good lives with sound sleep and wakefulness may be clarified through studies in which clinical- and daily-life findings in man and experimental data derived from animal studies are compared and comprehended.

研究发现，作用于大鼠基底前脑吻部的前列腺素E_2通过激活EP_4受体促进慢波睡眠，而通过激活EP_2和EP_4受体而增加异相睡眠(PS；或快速眼动睡眠：REM睡眠)。我们先前发现，一氧化氮供体化合物直接给药可降低PS，而NO合酶(NOS)抑制剂可增加PS，作用部位位于丘脑中线核、下丘脑外侧区和下丘脑后吻部或该区域的一部分。本研究利用c-Fos免疫组织化学方法显示，丘脑和下丘脑室旁核-前部、下丘脑室旁核-下丘脑后部、视交叉上核等核团神经元参与了NO供体化合物和NOS抑制剂引起的PS变化。此外，我们还在大鼠体内观察到脑内下丘脑下丘脑-1(食欲素A)的昼夜波动。该项目的一名成员渡边成功地提取并鉴定了一种新的PGE合成酶，该酶被发现也存在于哺乳动物的大脑中。在黑田东彦和Emura领导的临床调查中，已经研究了许多睡眠-觉醒障碍的病例。通过比较和理解人类的临床和日常生活发现以及动物研究得出的实验数据，有望阐明睡眠-觉醒障碍的病理生理学基础以及意识恶化的各种情况，以及过上健康睡眠和清醒的良好生活的艺术。