在外围组织中,通过葡萄糖皮质体信号来重置昼夜时间
A Balsalobre1, S A Brown, L Marcacci
1Département de Biologie Moléculaire, Sciences II, Université de Genève, 30 Quai Ernest Ansermet, CH-1211 Genève, Switzerland.
概括
德克萨米他是一种葡萄糖皮质激素类似物,可以在哺乳动物中重置外周昼夜时钟,但不能重置中枢大脑节律器. 外围时钟一整天都能响应相位重置,与中央时钟不同.
科学领域:
- 时间生物学 时间生物学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 哺乳动物的昼夜节律是由上神核 (SCN) 中央节律器和各种组织中的外周振荡器调节的.
- 了解中央和外围时钟的不同调节对于理解整体昼夜平衡至关重要.
研究的目的:
- 为了研究葡萄糖皮质类药物类似的德克萨米他对周围组织和中央SCN的昼夜基因表达的影响.
- 为了描述外围时钟对甲的反应中的相位重置特性.
主要方法:
- 培养的老鼠-1纤维细胞被用来评估德克萨梅他对昼夜基因表达的影响.
- 完整的动物被用德克萨梅他治疗,以评估肝脏,脏和心脏组织以及SCN神经元的相位变化.
- 为外围时钟生成相位移响应曲线.
主要成果:
- 德克萨米他诱导了培养纤维细胞中的昼夜基因表达.
- 德克萨米他会在外围组织 (肝脏,脏,心脏) 中引起短暂的相位变化,但在SCN神经元中不会.
- 周围昼夜振荡器在一天中表现出持续响应阶段重置的反应.
结论:
- 像德克萨米他这样的葡萄皮质激素可以差异调节中央和外围的昼夜钟.
- 与中央SCN时钟相比,外围时钟对相位重置刺激的敏感度更大.
- 这些发现凸显了外围昼夜振荡器的明显可塑性.
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