Social Regulation of Circadian Output Systems

昼夜节律输出系统的社会调节

• 批准号: 6766549
• 负责人: PHILIP K STODDARD
• 金额: $ 20.93万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6766549
• 关键词: adrenocorticotropic hormone; alternatives to animals in research; behavior test; behavioral /social science research tag; circadian rhythms; electrophysiology; environmental stressor; enzyme linked immunosorbent assay; ethology; fish; fish electric organ; genetically modified animals; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; male; neurochemistry; physiologic stressor; serotonin; socioenvironment

Circadian rhythms are often disrupted with advancing age and under conditions of stress, including social stress. Breakdown in human circadian rhythms are believed to occur most often downstream of the central circadian oscillator. Our lab has developed electric fish as a powerful non-mammalian vertebrate model system in which controlled changes in the social environment alter predictably the magnitude of two circadian rhythms in electric signal waveform parameters. Our system makes a valuable model because we have identified multiple social conditions that modulate circadian rhythm expression in multiple ways. As with mammalian models, situations promising social upheaval disrupt the circadian outputs. Social isolation, however, causes a progressive diminution of these rhythms, as though the coupling between the central oscillator and the peripheral effector had been weakened or broken. Restoration of favorable social conditions restores the strength of the rhythms. We have made significant progress in identifying the neurochemical components of the circadian output pathway. Two neurochemical messengers, 5-HT and ACTH, modulate the behavioral outputs, ACTH at the level of the peripheral effector organ. Results with males indicate that the circadian rhythms are regulated somewhere downstream of serotonin. We also have found that non-aromatizable androgens can enhance the amplitude of these circadian rhythms in a manner resembling certain favorable social manipulations. Building on our progress to date, we propose specific aims (1) to better understand the behavioral conditions that regulate circadian rhythms in the electric waveform, (2) to elucidate the roles of androgens and glucocorticoids in regulating the circadian rhythms, and (3) to identify which hormones of the hypothalamus-pituitary-adrenal axis are in direct control of the circadian outputs. Because the neuroanatomy and neurochemistry of the circadian control pathway have been conserved across vertebrate evolution, these studies will lead directly to testable hypotheses about mechanisms !underlying circadian rhythm pathologies in mammals, including humans.

昼夜节律通常会因年龄和压力条件（包括社会压力）而受到破坏。据信，人类昼夜节律的崩溃最常发生在中央昼夜节律振荡器的下游。我们的实验室已经开发了电鱼作为强大的非哺乳动物脊椎动物模型系统，在该系统中，社会环境中受控的变化可预测地改变了电信号波形参数中两个昼夜节律的幅度。我们的系统成为一个宝贵的模型，因为我们已经确定了多种以多种方式调节昼夜节律表达的社会条件。与哺乳动物模型一样，有望使社会动荡的情况破坏了昼夜节律的产量。然而，社会隔离会导致这些节奏的逐渐减少，好像中心之间的耦合 振荡器和外围效应子已被削弱或破裂。恢复有利的社会条件可以恢复节奏的力量。我们在识别昼夜节律途径的神经化学成分方面取得了重大进展。两个神经化学的使者（5-HT和ACTH）调节行为输出，ACTH在外围效应器官的水平上。男性的结果表明昼夜节律受调节，在5-羟色胺下游的某个地方。我们还发现，不可芳香的雄激素可以以类似于某些有利的社会操纵的方式增强这些昼夜节律的幅度。 Building on our progress to date, we propose specific aims (1) to better understand the behavioral conditions that regulate circadian rhythms in the electric waveform, (2) to elucidate the roles of androgens and glucocorticoids in regulating the circadian rhythms, and (3) to identify which hormones of the hypothalamus-pituitary-adrenal axis are in direct control of the circadian outputs.由于昼夜节律控制途径的神经解剖学和神经化学在脊椎动物进化过程中得到了保守，因此这些研究将直接导致有关机制的可检验的假设！包括人类在内的哺乳动物中的昼夜节律病理学基础。