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Development of Chronotherapy Based on Clock Genes

基于时钟基因的计时疗法的发展

基本信息

批准号：
13672391
负责人：
OHDO Shigehiro
金额：
$ 2.3万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672391/
关键词：
Biological Rhythm Clock genes Suprachiasmatic Nuclei Chronopharmacology Chronopharmacokinetics マウス

项目摘要

Mammal ians circadian pacemaker resides in the paired suprachiasmatic nuclei (SCN). Clock genes are the genes that control the circadian rhythms in physiology and behavior. The effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-hr rhythms of biochemical, physiological and behavioral processes under the control of circadian clock. However, many drugs are still given without regard to the time of day. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. In the present study, the following points were clarified. To monitor the rhythmic marker may be useful to choose the most appropriate time of day for administration of drugs that may increase their therapeutic effects and/or reduce their side effects. Also, we showed the disruptive effect of interferon on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and SCN. The alteration of the clock function, a new concept of adverse effects, can be overcome by devising a dosing schedule that minimizes adverse drug effects on clock function. Furthermore, to produce new rhythmicity by manipulating the conditions of living organs by using rhythmic administration of altered feeding schedules or several drugs maylead to the new concept of chronopharmacotherapy.

哺乳动物的昼夜节律起搏器位于成对的视交叉上核（SCN）中。时钟基因是控制生理和行为昼夜节律的基因。许多药物的有效性和毒性取决于给药时间，而给药时间与生物钟控制下的生化、生理和行为过程的 24 小时节律相关。然而，许多药物的给药仍然不考虑一天中的时间。识别用于选择给药时间的节律标记将导致时间药物疗法的进展和扩散的改善。在本研究中，澄清了以下几点。监测节律标记可能有助于选择一天中最合适的给药时间，这可以增加其治疗效果和/或减少其副作用。此外，我们还发现干扰素对外周和视交叉上核的运动活动节律、体温和时钟基因 mRNA 表达具有破坏作用。时钟功能的改变是不良反应的一个新概念，可以通过设计给药方案来克服，以尽量减少药物对时钟功能的不良影响。此外，通过改变喂养计划或几种药物的节律性给药来操纵活器官的状况来产生新的节律性可能会导致时间药物疗法的新概念。