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Possibility that nitric oxide has a role in the regulation of sleep and consciousness

一氧化氮可能在睡眠和意识调节中发挥作用

基本信息

批准号：
14570950
负责人：
MATSUMURA Hitoshi
金额：
$ 2.11万
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：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570950/
关键词：
nitric oxide brain REM sleep consciousness microdialysis

项目摘要

The head investigator of this research project and his coworkers found that N^6-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), increased REM sleep when administered to the diencephalon of a rat. On the other hand, NOC 12, a nitric oxide (NO) donor compound, decreased REM sleep when administered to the same region. Based on these and other results, we assumed that NO has a role in the diencephalon to regulate REM sleep. It might be further conceived that NO is involved in pathophysiology of altered consciousness and attentional disturbances. However, it is still obscure whether the REM sleep changes were attributed to quantitative changes in NO in the diencephalon or some other unknown effects of L-NAME and NOC 12. Therefore, we investigated in this project whether the level of NO in the diencephalon changes along with a circadian sleep-wake rhythm and whether L-NAME causes a decrease in the level of NO in the diencephalon. We performed surgical operation to rats to implant electrodes to record EEG, EMG and EOG (electrooculogram) and two microdialysis probes to measure the level of NO in the diencephalon and to administer L-NAME to the same region. After full recovery from the surgery for 1 week, electrodes and microdialysis probes of each rat were connected to respective equipments. The level of NO in the rat diencephalon indicated a circadian rhythm, high during night, active period of rats, and low during day when rats spend time sleeping. When L-NAME was administered to the diencephalon, the level of NO showed a decrease. Our results supported the hypothesis that NO in the diencephalon is involved in the regulation of REM sleep. It remains to be studied whether NO is also involved in pathophysiology of altered consciousness and attentional disturbances.

该研究项目的首席研究员和他的同事发现，当将N^6-硝基-L-精氨酸甲酯（L-NAME）（一氧化氮合酶（NOS）的抑制剂）注射到大鼠的间脑时，可以增加REM睡眠。另一方面，NOC 12，一种一氧化氮（NO）供体化合物，当给予同一区域时，减少了REM睡眠。基于这些和其他结果，我们假设NO在间脑中具有调节REM睡眠的作用。这可能是进一步设想，NO参与的病理生理学改变的意识和注意力障碍。然而，REM睡眠的变化是否归因于间脑中NO的定量变化或L-NAME和NOC 12的其他未知作用仍不清楚。因此，在本项目中，我们调查间脑中的NO水平是否沿着昼夜睡眠-觉醒节律而变化，以及L-NAME是否导致间脑中的NO水平降低。采用手术方法植入电极记录大鼠的EEG、EMG和EOG（眼电图），植入两个微透析探针测定间脑中NO的含量，并在同一区域注射L-NAME。手术完全恢复1周后，将每只大鼠的电极和微透析探针连接到相应的设备。大鼠间脑中NO含量呈昼夜节律变化，夜间活动期高，白天睡眠期低。间脑注射L-NAME后，NO水平降低。我们的研究结果支持了间脑中NO参与REM睡眠调节的假设。NO是否也参与意识改变和注意力障碍的病理生理还有待研究。