Neuropeptide signaling differentially affects phase maintenance and rhythm generation in SCN and extra-SCN circadian oscillators.
Neuropeptide signaling differentially affects phase maintenance and rhythm generation in SCN and extra-SCN circadian oscillators.
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DOI：
10.1371/journal.pone.0018926
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Piggins HD
中科院分区：
文献类型：
--
作者：
Hughes AT;Guilding C;Piggins HD
生理和行为的昼夜节律是由位于下丘脑视交叉上核（SCN）的大脑主导昼夜节律起搏器协调的。血管活性肠肽（VIP）及其受体VPAC 2在SCN起搏功能中起重要作用。缺乏VPAC 2受体（Vipr 2 −/−）的小鼠表现出行为和代谢节律的破坏，并显示出SCN神经元活动和时钟基因表达的改变。在脑内，SCN不是含有内源性昼夜节律振荡器的唯一位点，也不是VPAC 2受体表达的唯一位点; VPAC 2受体和节律时钟基因/蛋白质表达都已在内侧基底下丘脑的弓状核（Arc）和背内侧核（DMH）以及垂体中发现。然而，VPAC 2受体在这些组织中节律产生和维持的功能作用尚不清楚。我们使用野生型（WT）和表达荧光素酶报告基因（PER 2：：LUC）的Vipr 2 −/−小鼠来研究这些额外SCN组织中时钟基因蛋白PER 2的昼夜节律是否因缺乏VPAC 2受体而受损。Vipr 2 −/− SCN培养物表达的PER 2：：LUC振荡幅度显著低于WT SCN。令人惊讶的是，在Vipr 2 −/− Arc/ME/PT复合体（Arc、正中隆起和结节部）、DMH和垂体中，节律的周期、振幅和阻尼率与WT没有显著差异。有趣的是，虽然我们发现WT SCN和Arc/ME/PT组织在培养时保持一致的昼夜节律时相，但相应的Vipr 2 −/−培养物的时相通过剔除/培养程序重置。这些数据表明，虽然Vipr 2 −/−小鼠中维持了SCN外昼夜节律振荡的主要节律参数，但这些振荡器抵抗相移的能力受到了损害。这些缺陷可能导致与Vipr 2 −/−动物相关的异常行为和代谢。此外，我们的数据表明昼夜节律强度和组织抵抗昼夜节律相位重置的能力之间的联系。
Circadian rhythms in physiology and behavior are coordinated by the brain's dominant circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Vasoactive intestinal polypeptide (VIP) and its receptor, VPAC2, play important roles in the functioning of the SCN pacemaker. Mice lacking VPAC2 receptors (Vipr2−/−) express disrupted behavioral and metabolic rhythms and show altered SCN neuronal activity and clock gene expression. Within the brain, the SCN is not the only site containing endogenous circadian oscillators, nor is it the only site of VPAC2 receptor expression; both VPAC2 receptors and rhythmic clock gene/protein expression have been noted in the arcuate (Arc) and dorsomedial (DMH) nuclei of the mediobasal hypothalamus, and in the pituitary gland. The functional role of VPAC2 receptors in rhythm generation and maintenance in these tissues is, however, unknown. We used wild type (WT) and Vipr2−/− mice expressing a luciferase reporter (PER2::LUC) to investigate whether circadian rhythms in the clock gene protein PER2 in these extra-SCN tissues were compromised by the absence of the VPAC2 receptor. Vipr2−/− SCN cultures expressed significantly lower amplitude PER2::LUC oscillations than WT SCN. Surprisingly, in Vipr2−/− Arc/ME/PT complex (Arc, median eminence and pars tuberalis), DMH and pituitary, the period, amplitude and rate of damping of rhythms were not significantly different to WT. Intriguingly, while we found WT SCN and Arc/ME/PT tissues to maintain a consistent circadian phase when cultured, the phase of corresponding Vipr2−/− cultures was reset by cull/culture procedure. These data demonstrate that while the main rhythm parameters of extra-SCN circadian oscillations are maintained in Vipr2−/− mice, the ability of these oscillators to resist phase shifts is compromised. These deficiencies may contribute towards the aberrant behavior and metabolism associated with Vipr2−/− animals. Further, our data indicate a link between circadian rhythm strength and the ability of tissues to resist circadian phase resetting.
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DOI：
10.1523/jneurosci.3801-08.2009
发表时间：
2009-02-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ciarleglio CM;Gamble KL;Axley JC;Strauss BR;Cohen JY;Colwell CS;McMahon DG
通讯作者：
McMahon DG
影响因子：
3.6
作者：
Guilding, Clare;Hughes, Alun T. L.;Piggins, Hugh D.
通讯作者：
Piggins, Hugh D.
影响因子：
5.3
作者：
Abe, M;Herzog, ED;Block, GD
通讯作者：
Block, GD
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
影响因子：
3.4
作者：
Dragich, Joanna M.;Loh, Dawn H.;Colwell, Christopher S.
通讯作者：
Colwell, Christopher S.