The influence of neuronal electrical activity on the mammalian central clock metabolome
The influence of neuronal electrical activity on the mammalian central clock metabolome
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DOI：
10.1007/s11306-018-1423-z
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发表时间：
2018-10-01
期刊：
影响因子：
3.6
通讯作者：
Michel, Stephan
中科院分区：
文献类型：
--
作者：
Buijink, M. Renate;van Weeghel, Michel;Michel, Stephan
大多数生物在生理和行为上都表现出昼夜节律。在哺乳动物中，这些节律是由视交叉上核（SCN）协调的。最近，一些代谢物被认为是昼夜节律的重要调节因子。代谢组学方法有助于识别外周组织昼夜节律过程中的一些关键代谢物，但目前缺乏常规测量小脑区域代谢物的方法。目的建立一种可靠的中央生物钟代谢物定量方法，并将其与神经元兴奋性的不同状态联系起来。方法建立了一种适用于液相色谱-质谱联用的脑组织小样本（0.2 mm(3)）采集和处理方法。对SCN及其主要下丘脑靶点室旁核（PVN）的代谢物进行了分析。在SCN电活动内源性节律的高峰（中午）和低谷（午夜）采集组织样本。此外，神经活性在药理学上也发生了改变。结果我们发现白天/夜间的电活动波动或白天的沉默活动的影响很小。相反，夜间增加的电活动显著上调了SCN和PVN中的许多代谢物。结论本方法可从小脑样本中获得可靠的生理相关代谢物数据。在夜间诱导电活动模拟了SCN中光脉冲的效果，产生了昼夜节律的相移。代谢物的上调可能在这一过程中具有功能作用，因为它们不仅仅是生理状态的产物，它们是细胞信号通路的重要组成部分。
Introduction Most organisms display circadian rhythms in physiology and behaviour. In mammals, these rhythms are orchestrated by the suprachiasmatic nucleus (SCN). Recently, several metabolites have emerged as important regulators of circadian timekeeping. Metabolomics approaches have aided in identifying some key metabolites in circadian processes in peripheral tissue, but methods to routinely measure metabolites in small brain areas are currently lacking.Objective The aim of the study was to establish a reliable method for metabolite quantifications in the central circadian clock and relate them to different states of neuronal excitability.Methods We developed a method to collect and process small brain tissue samples (0.2 mm(3)), suitable for liquid chromatography-mass spectrometry. Metabolites were analysed in the SCN and one of its main hypothalamic targets, the paraventricular nucleus (PVN). Tissue samples were taken at peak (midday) and trough (midnight) of the endogenous rhythm in SCN electrical activity. Additionally, neuronal activity was altered pharmacologically.Results We found a minor effect of day/night fluctuations in electrical activity or silencing activity during the day. In contrast, increasing electrical activity during the night significantly upregulated many metabolites in SCN and PVN.Conclusion Our method has shown to produce reliable and physiologically relevant metabolite data from small brain samples. Inducing electrical activity at night mimics the effect of a light pulses in the SCN, producing phase shifts of the circadian rhythm. The upregulation of metabolites could have a functional role in this process, since they are not solely products of physiological states, they are significant parts of cellular signalling pathways.