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Crosstalk of signal transduction in sleep-wake regulation

睡眠-觉醒调节中信号转导的串扰

基本信息

批准号：
18300129
负责人：
HAYASHI Osamu
金额：
$ 10.47万
依托单位：
Osaka Bioscience Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18300129/
关键词：
leep-wake cycle sleep substances neural network humoral regulation

项目摘要

Administration of SeC14, a selective inhibitor of prostaglandin (PG) D synthase (PGDS), inhibited sleep dose-dependently in wild-type or hematopoietic PGDS knockout (KO) mice but not at all in lipocalin-type PGDS KO, hematopoietic and lipocalin-type PGDS double KO or PGD receptor (DP1R) KO mice. Furthermore, the DP1R antagonist reduced sleep of rats during infusion into the subarachnoid space under the rostral basal forebrain. These results clearly show that lipocalin-type PGDS/PGD2/DP1R system plays pivotal roles in the regulation of physiological sleep.PGD_2 promotes sleep by activation of a sleep-center in the ventrolateral pre-optic area, and suppression of the wake-center in the histaminergic tuberomammillary nucleus (TMN). When we examined sleep-wake cycles of histamine H_1 receptors (H_1R) KO mice, H_1R KO mice showed sleep-wake cycles with fewer incidents of brief awakening, indicating that H_1R was involved in the regulation of behavioral state transitions from non-rapid eye movement (NREM) sleep to wakefulness.Histaminergic TMN contains adenosine deaminase. Inhibition of adenosine deaminase or activation of adenosine A_1 receptor in the TMN increased NREM sleep and suppressed the histamine release in the brain. These results that indicate adenosine suppresses histaminergic activity and induces NREM sleep via A_1 receptors.Histaminergic system had been implicated in the arousal effect of modafinil. However, we found that modafinil induced wakefulness in both H_1R KO and wild-type mice, indicating that histaminergic system was not essential for the modafinil-induced wakefulness. However, dopamine D_2 receptor KO mice exhibited attenuated modafinil-induced wakefulness. Moreover, pretreatment of D_2 receptor KO mice with Di receptor antagonist completely abolished arousal effects of modafinil. These findings indicate that the dopaminergic D_1 and D_2 receptor are essential for the wakefulness induced by modafinil.

前列腺素D合成酶(PGDS)选择性抑制剂SeC14可剂量依赖性地抑制野生型或造血型PGDS基因敲除(KO)小鼠的睡眠，但对Lipocalin型、造血型和Lipocalin型PGDS双KO或PGD受体(DP1R)KO小鼠无明显影响。此外，DP1R拮抗剂在向大鼠基底前脑吻侧下蛛网膜下腔注射期间减少了大鼠的睡眠。这些结果清楚地表明，Lipocalin型PGDS/PGD2/DP1R系统在生理睡眠调节中起着关键作用。PGD2通过激活视前腹外侧区的睡眠中心和抑制组胺能结节乳头核(TMN)的觉醒中心来促进睡眠。当我们研究组胺H_1受体(H_1R)KO小鼠的睡眠-觉醒周期时，H_1R KO小鼠表现出睡眠-唤醒周期，短暂觉醒事件较少，这表明H_1R参与了从非快速眼动(NREM)睡眠到清醒的行为状态转换的调节。抑制TMN中腺苷脱氨酶或激活腺苷A_1受体可增加NREM睡眠，抑制脑内组胺释放。这些结果表明，腺苷通过A_1受体抑制组胺能活动并诱导NREM睡眠，组胺能系统参与莫达非尼的唤醒作用。然而，我们发现莫达非尼在H_1R KO和野生型小鼠中都能诱导觉醒，这表明组胺能系统在莫达非尼诱导的觉醒中不是必需的。然而，多巴胺D_2受体KO小鼠表现出莫达非尼诱导的觉醒减弱。D2受体拮抗剂可完全阻断莫达非尼的唤醒作用。这些结果表明，多巴胺能D_1和D_2受体在莫达非尼诱发觉醒过程中起重要作用。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of prostaglandin D2 in the homeostatic and circadian regulation of sleep

前列腺素 D2 在睡眠稳态和昼夜节律调节中的作用

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Urade Y;Eguchi N;Hayaishi O.;早石修;早石修;早石修;Osamu Hayaishi;Osamu Hayaishi;Osamu Hayaishi;早石修;Osamu Hayaishi;Osamu Hayaishi
通讯作者：
Osamu Hayaishi

眠りを科学する

睡眠科学

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Urade Y;Eguchi N;Hayaishi O.;早石修;早石修
通讯作者：
早石修

Role of prostaglandin D_2 in the homeostatic and circadian regulation of sleep

前列腺素 D_2 在睡眠稳态和昼夜节律调节中的作用

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Urade Y;Eguchi N;Hayaishi O.;早石修;早石修;早石修;Osamu Hayaishi;Osamu Hayaishi;Osamu Hayaishi;早石修;Osamu Hayaishi
通讯作者：
Osamu Hayaishi

Prostaglandins and the regulation of sleep and wakefulness.

前列腺素与睡眠和觉醒的调节。