A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus
A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus
复制标题
DOI：
10.1186/1756-6606-2-28
复制
发表时间：
2009-01-01
期刊：
影响因子：
3.6
通讯作者：
Piggins, Hugh D.
中科院分区：
文献类型：
--
作者：
Guilding, Clare;Hughes, Alun T. L.;Piggins, Hugh D.
背景资料：在哺乳动物中，视交叉上核（SCN）中细胞自主时钟的同步活动使该结构能够作为主昼夜节律钟发挥作用，协调生理和行为中的日常节律。然而，这种生物钟的主导地位受到了以下观察结果的挑战：代谢胁迫可以超越SCN控制的节律，并且生物钟基因在许多大脑区域中表达，包括那些与食欲和进食调节有关的区域。最近的发展，小鼠中的时钟基因/蛋白质的活动报告的生物发光结构（荧光素酶或luc），现在使我们能够跟踪分子振荡在许多组织离体。因此，我们确定了两个时钟活动和响应代谢扰动的细胞和组织内的内侧基底下丘脑（MBH），一个关键的网站，为最佳的内部稳态regulation.Results：在这里，我们证明了内源性昼夜节律的PER 2：：LUC表达的离散细分的弓状核（弧）和背内侧核（DMH）。单细胞的节律不能保持长期的同步，导致细胞和组织水平的振荡衰减。互补的电生理记录揭示了Arc和DMH神经元活动的节律。此外，在第三脑室室管膜层和正中隆起/结节部（ME/PT）中检测到PER 2：：LUC节律。高脂饮食对MBH中的分子振荡没有影响，而食物剥夺导致ME/PT中的相位改变。我们的结果提供了第一个单细胞分辨率的内源性昼夜节律的时钟基因表达在任何完整的组织以外的SCN，揭示了细胞基础的组织水平阻尼extra-SCN振荡器，并证明了振荡器在ME/PT对代谢变化有反应。
Background: In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN) enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many brain areas, including those implicated in the regulation of appetite and feeding. The recent development of mice in which clock gene/protein activity is reported by bioluminescent constructs (luciferase or luc) now enables us to track molecular oscillations in numerous tissues ex vivo. Consequently we determined both clock activities and responsiveness to metabolic perturbations of cells and tissues within the mediobasal hypothalamus (MBH), a site pivotal for optimal internal homeostatic regulation.Results: Here we demonstrate endogenous circadian rhythms of PER2::LUC expression in discrete subdivisions of the arcuate (Arc) and dorsomedial nuclei (DMH). Rhythms resolved to single cells did not maintain long-term synchrony with one-another, leading to a damping of oscillations at both cell and tissue levels. Complementary electrophysiology recordings revealed rhythms in neuronal activity in the Arc and DMH. Further, PER2:: LUC rhythms were detected in the ependymal layer of the third ventricle and in the median eminence/pars tuberalis (ME/PT). A high-fat diet had no effect on the molecular oscillations in the MBH, whereas food deprivation resulted in an altered phase in the ME/PT.Conclusion: Our results provide the first single cell resolution of endogenous circadian rhythms in clock gene expression in any intact tissue outside the SCN, reveal the cellular basis for tissue level damping in extra-SCN oscillators and demonstrate that an oscillator in the ME/PT is responsive to changes in metabolism.