Basic and Clinical Studies on Humoral Control of Sleep

睡眠体液控制的基础与临床研究

• 批准号: 01480279
• 负责人: KATO Nobumasa
• 金额: $ 3.65万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480279/
• 关键词: DSIP; Dopamine; Serotonin; Growth hormone; Thyroid-stimulating hormone; Prolactin; Circadian rhythm; Thermoregulation

The humoral control of sleep mechanisms was investigated in terms of 1) possible roles of delta sleep-inducing peptide (DSIP) as one of slow-wave promoting substances, and 2) secretary pattern of growth hormone (GH) during slow wave sleep (SWS).A sensitive enzyme immunoassay (EIA) method for measuring DSIP in body fluids was developed in the laboratory. This method was unable to detect DSIP-like material in human and rat tissues. Plasma DSIP levels were measured throughout 24 h in healthy male subjects and diurnal variations of circulatory DSIP concentrations were found. Besides its known sleep-promoting effect, we found the thermoregulatory action of DSIP in rats. DSIP as well as its phosphorylated form (P-DSIP) was found to potentiate dopamine- or serotonin-induced hypothermia in rats at the ambient temperature. Pharmacological study showed this thermoregulatory action of DSIP was exerted via 5-HT 1A receptors. Zopiclone, one of non-benzodiazepine hypnotics was demonstrated to increa … More se DSIP contents in the rat brain dose-dependently. These findings may further present significant roles of DSIP in modulating sleep and sleep-related phenomena.An ultra-sensitive EIA method of human GH was introduced to evaluate 24 h secretary pattern in normal condition and in sleep-deprived condition. The lowest level of basal plasma GH was as low as 10 pg/ml, which could be detected for the first time by this method. Twenty-four hour secretory rhythm of GH in normal and delayed sleep phase suggested the presence of ultradian rhythm in GH secretion. Prolactin and thyroid-stimulating hormone (TSH) were also measured in the same samples. Prolactin was found to be elevated during sleep and prolactin secretion appeared to be promoted after REM sleep. Furthermore, the relationship between hormone secretion and initiation of the first SWS was studied in more detail by frequent determinations of plasma GH and prolactin in 5-min intervals. GH secretion increased 10 min after the initiation of SWS, and the pattern of prolactin secretion was found to be almost identical with GH secretion. Namely, GH secretion, prolactin secretion and the first SWS processes were somehow synchronized one another with a short delay. TSH secretion had its own secretory pattern with higher values during night, which normally was inhibited by sleep. Less

本文主要从慢波促进物质delta睡眠诱导肽（DSIP）在慢波睡眠中可能发挥的作用和生长激素（GH）在慢波睡眠中的分泌模式两方面探讨了睡眠的体液调控机制。建立了一种灵敏的酶免疫分析法（EIA）测定体液中DSIP的方法。该方法无法检测到人和大鼠组织中的dsip样物质。在24小时内测量健康男性受试者血浆DSIP水平，发现循环DSIP浓度的日变化。除了已知的促进睡眠作用外，我们还发现了DSIP在大鼠体内的体温调节作用。DSIP及其磷酸化形式（P-DSIP）被发现在环境温度下增强多巴胺或血清素诱导的大鼠低温。药理研究表明，DSIP通过5-HT 1A受体发挥体温调节作用。Zopiclone是一种非苯二氮卓类催眠药，可以增加大鼠脑内的DSIP含量。这些发现可能进一步表明DSIP在调节睡眠和睡眠相关现象中的重要作用。介绍了一种超灵敏的人生长激素EIA方法，用于评价正常和睡眠剥夺条件下24 h分泌模式。基础血浆GH最低可达10 pg/ml，为首次检测到。正常和延迟睡眠期生长激素24小时分泌节律提示生长激素分泌存在超昼夜节律。在相同的样本中也测量了催乳素和促甲状腺激素（TSH）。研究发现，睡眠时催乳素水平升高，而快速眼动睡眠后催乳素的分泌似乎有所增加。此外，通过每隔5分钟频繁检测血浆GH和催乳素，更详细地研究了激素分泌与第一次SWS发生之间的关系。SWS开始后10 min生长激素分泌增加，泌乳素分泌模式与生长激素分泌模式基本一致。也就是说，生长激素分泌、催乳素分泌和第一个SWS过程以某种方式相互同步，并有短暂的延迟。TSH分泌有其自身的分泌模式，夜间较高，通常受睡眠抑制。少

项目成果

定松 美幸,飯田 英晴,加藤 進昌,橋田 誠一,石川 栄治: "高感度酵素免疫測定法によるヒト成長ホルモン分泌リズムの睡眠依存性の再検討" 脳と精神の医学. 1. 21-27 (1990)

Miyuki Sadamatsu、Hideharu Iida、Nobumasa Kato、Seiichi Hashida、Eiji Ishikawa：“使用高灵敏度酶免疫分析重新检查人类生长激素分泌节律的睡眠依赖性”《脑与精神病学杂志》1. 21-27 (1990)。

綱島 浩一,山寺 博史,加藤 進昌,ミツシタ 洋,高橋 清久: "ゾピクロン投与によるラット脳内および血中デルタ睡眠誘発ペプチド様免疫活性(DSIPーLI)の変化" 脳と精神の医学. 3. (1992)

Koichi Tsunashima、Hiroshi Yamadera、Nobumasa Kato、Hiroshi Mitsushita、Kiyohisa Takahashi：“佐匹克隆给药导致大鼠大脑和血液中 Delta 睡眠诱导的肽样免疫活性 (DSIP-LI) 的变化”《大脑与精神病学医学》3。（ 1992))

Kato N. et al.: "Endocrinological approach to sleep disorders." Clinical Neuroscience. 9. 1062-1065 (1991)

Kato N. 等人：“睡眠障碍的内分泌学方法。”

Tsunashima K,Masui A,and Rato N.: "The effect of delta sleep-inducing pepride(DSIP)and phosphorylated DSIP(P-DSIP)on the apomorphine-induced hypothermia in rats." Brain Research. 510. 171-174 (1990)

Tsunashima K、Masui A 和 Rato N.：“Delta 睡眠诱导肽 (DSIP) 和磷酸化 DSIP (P-DSIP) 对阿扑吗啡引起的大鼠体温过低的影响。”

Iida H. et al: "Sleep dependency of the secretory rhythm of human prolactin on the correlation with REM-NREM cycles." Brain Sci Ment Dis. 2. 265-271 (1991)

Iida H. 等人：“人类催乳素分泌节律的睡眠依赖性与 REM-NREM 周期的相关性。”