Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei
Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei
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DOI：
10.1152/ajpregu.90463.2008
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发表时间：
2009-03-01
影响因子：
2.8
通讯作者：
Zhou, Qun-Yong
中科院分区：
文献类型：
--
作者：
Li, Jia-Da;Burton, Katherine J.;Zhou, Qun-Yong
李建东，伯顿，张聪，胡SB，周庆英。加压素受体V1 a调节运动活动的昼夜节律和视交叉上核中钟控基因的表达。Am J Physiol Regul Integr Comp Physiol 296：R824-R830，2009。首次发表于2008年12月3日; doi：10.1152/ajpregu.90463.2008。视交叉上核（SCN）是协调哺乳动物日常行为和生理周期的主要昼夜节律起搏器。一个转录和翻译反馈环网络是SCN神经元内昼夜节律振荡的操作分子机制的基础。目前尚不清楚时间信息是如何从SCN神经元传递到最终唤起昼夜节律的。SCN和其靶神经元之间的细胞间通讯对于产生连贯的昼夜节律至关重要。在分子水平上，由时钟控制基因编码的神经肽被认为是重要的输出介质。精氨酸加压素（AVP）就是这样一种生物钟控制基因的产物。先前的研究已经证明了脑脊液和SCN中AVP水平的昼夜节律。AVP的生理效应由三种类型的AVP受体介导，命名为V1 a，V1 b和V2。在这项研究中，我们报告说，V1 a mRNA水平显示在SCN的昼夜节律，在夜间达到峰值。在V1 a缺陷（V1 a（-/-））小鼠中，运动活动的昼夜节律性显著降低（快速傅立叶变换功率降低50-75%）。然而，光掩蔽和光诱导的相移效应在V1 a（-/-）小鼠中是完整的。尽管时钟核心基因的表达没有改变，但V1 a（-/-）小鼠SCN中前动力蛋白2（PK 2）mRNA振荡的昼夜节律幅度减弱（类似于峰值水平降低50%）。体外实验表明AVP通过V1 a受体作用于PK 2启动子，能够增强其转录活性。因此，这些研究表明，AVP-V1 a信号在产生明显的昼夜节律中起着重要作用。
Li JD, Burton KJ, Zhang C, Hu SB, Zhou QY. Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei. Am J Physiol Regul Integr Comp Physiol 296: R824-R830, 2009. First published December 3, 2008; doi:10.1152/ajpregu.90463.2008.-The suprachiasmatic nuclei (SCN) serve as the principal circadian pacemakers that coordinate daily cycles of behavior and physiology for mammals. A network of transcriptional and translational feedback loops underlies the operating molecular mechanism for circadian oscillation within the SCN neurons. It remains unclear how timing information is transmitted from SCN neurons to eventually evoke circadian rhythms. Intercellular communication between the SCN and its target neurons is critical for the generation of coherent circadian rhythms. At the molecular level, neuropeptides encoded by clock-controlled genes have been indicated as important output mediators. Arginine vasopressin (AVP) is the product of one such clock-controlled gene. Previous studies have demonstrated a circadian rhythm of AVP levels in the cerebrospinal fluid and the SCN. The physiological effects of AVP are mediated by three types of AVP receptors, designated as V1a, V1b, and V2. In this study, we report that V1a mRNA levels displayed a circadian rhythm in the SCN, peaking during night hours. The circadian rhythmicity of locomotor activities was significantly reduced in V1a-deficient (V1a(-/-)) mice (50-75% reduction in the power of fast Fourier transformation). However, the light masking and light-induced phase shift effects are intact in V1a(-/-) mice. Whereas the expression of clock core genes was unaltered, the circadian amplitude of prokineticin 2 (PK2) mRNA oscillation was attenuated in the SCN of V1a(-/-) mice (similar to 50% reduction in the peak levels). In vitro experiments demonstrated that AVP, acting through V1a receptor, was able to enhance the transcriptional activity of the PK2 promoter. These studies thus indicate that AVP-V1a signaling plays an important role in the generation of overt circadian rhythms.