Development of the mouse model with 24-hour rhythm disturbances

24小时节律紊乱小鼠模型的建立

• 批准号: 09672330
• 负责人: OHDO Shigehiro
• 金额: $ 1.86万
• 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: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672330/
• 关键词: Biological Rhythm; Chronopharmacology; Pharmacokinetics; Interferon; Suprachiasmatic nuclei; mouse; 視交叉上核

The effectiveness and toxicity of many drugs vary depending on the dosing schedule associated with the twenty-four hour rhythms of biochemical, physiological and behavioral processes. In contrast, several drugs can cause alterations to the twenty-four hour rhythms, which leads to illness and altered homeostatic regulation. However, the mechanism has not been clarified from the viewpoint of the disruptive effect of the drugs on clock genes. Here, we show the disruptive effect of interferon- α on the rhythm of locomotor activity, body temperature and clock genes mRNA expression in the periphery and suprachiasmatic nuclei, a primary circadian pacemaker. The rhythmicity of clock genes and the photic induction of the mPer1 gene in suprachiasmatic nuclei were disturbed by the repetitive administration of interferon- α. Furthermore, 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. Thus I developed the mouse model with twenty-four hour rhythm disturbances induced by interferon.

许多药物的有效性和毒性取决于与生化、生理和行为过程的24小时节律相关的给药方案。相比之下，一些药物可以导致24小时节律的改变，从而导致疾病和体内平衡调节的改变。然而，从药物对时钟基因的破坏作用的角度来看，其机制尚未阐明。在这里，我们展示了干扰素- α对运动活动的节律、体温和外周核和视交叉上核（一种主要的昼夜节律起搏器）中时钟基因mRNA表达的破坏性作用。干扰素- α的重复给药干扰了视交叉上核时钟基因的节律性和mPer 1基因的光诱导。此外，生物钟功能的改变，一种新的不良反应概念，可以通过设计一个给药方案，最大限度地减少药物对生物钟功能的不良影响来克服。因此，我开发了干扰素诱导的24小时节律紊乱的小鼠模型。

项目成果

Shigehiro Ohdo et al: "Circadian rhythm of fever induced by interferon-α."Life Sciences. 61 8. PL95-100 (1997)

Shigehiro Ohdo 等人：“干扰素-α 引起的发热的昼夜节律”。生命科学，61 8。PL95-100 (1997)。

Shigehiro Ohdo et al: "Basis for dosing time-dependent changes in the antiviral activity of interferon-α in Mice"The Journal of Pharmacology and Experimental Therapeutics. 294・2. 488-493 (2000)

Shigehiro Ohdo 等人：“小鼠中干扰素-α 的抗病毒活性的给药时间依赖性变化的基础”药理学和实验治疗学杂志 294·2（2000）。

Satoru Koyanagi et al: "Chronopharmacological study of interferon-α in mice"The Journal of Pharmacology and Experimental Therapeutics. 283・1. 259-264 (1997)

Satoru Koyanagi 等：“小鼠干扰素-α 的时间药理学研究”药理学和实验治疗学杂志 283·1（1997）。

Shigehiro Ohdo et al: "Circadian rhythm of fever induced by interferon-α in mice"Life Sciences. 61・8. PL95-100 (1997)

Shigehiro Ohdo 等人：“干扰素-α 引起小鼠发热的昼夜节律”生命科学 61・8（1997 年）。

Satoru Koyanagi et al: "Chronopharmacological study of interferon-α in mice."The Journal of Pharmacology and Experimental Therapeutics. 283 1. 259-264 (1997)

Satoru Koyanagi 等人：“小鼠干扰素-α 的时间药理学研究”。《药理学和实验治疗学杂志》283 1. 259-264 (1997)。