The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus
The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus
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DOI：
10.1111/j.1460-9568.2010.07119.x
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发表时间：
2010-03-01
影响因子：
3.4
通讯作者：
Colwell, Christopher S.
中科院分区：
文献类型：
--
作者：
Dragich, Joanna M.;Loh, Dawn H.;Colwell, Christopher S.
以前，我们已经证明，缺乏血管活性肠肽(VIP)或垂体腺苷环化酶激活多肽(PACAP)的小鼠在昼夜节律系统对光的行为反应中表现出特定的缺陷。在这项研究中，我们研究了视交叉上核(SCN)内分子时钟的光调节是如何因这些密切相关的多肽的丢失而改变的。在主观夜间，与野生型小鼠相比，VIP和PACAP缺陷小鼠SCN内FOS和磷酸化丝裂原活化蛋白激酶(p-MAPK)免疫反应细胞的光诱导强度均显著降低。在VIP基因缺陷的小鼠中，SCN中时钟基因PER1(PER1)的光诱导减少，但在PACAP缺陷的小鼠中没有。夜间FOS、p-MAPK或PER1的基线水平不因这些多肽的丢失而改变。相比之下，在主观白天，光照增加了VIP缺陷小鼠SCN中FOS、p-MAPK和PER1的水平，但在其他基因型鼠中没有。在这一阶段，与未经治疗的对照组相比，VIP缺陷小鼠的这些标记物的基线水平降低。最后，在主观夜晚，失去任何一种神经肽都会降低肾上腺中光诱发的PER1水平的增加幅度，而基线水平没有任何变化。综上所述，我们的结果表明，VIP和PACAP都调节SCN内细胞对光的反应。此外，在SCN内适当的时间门控光诱导的基因表达需要VIP，而不是PACAP。
Previously, we have shown that mice deficient in either vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit specific deficits in the behavioral response of their circadian system to light. In this study, we investigated how the photic regulation of the molecular clock within the suprachiasmatic nucleus (SCN) is altered by the loss of these closely-related peptides. During the subjective night, the magnitude of the light-induction of FOS and phosphorylated mitogen-activated protein kinase (p-MAPK) immunoreactive cells within the SCN was significantly reduced in both VIP- and PACAP-deficient mice when compared with wild-type mice. The photic induction of the clock gene Period1 (Per1) in the SCN was reduced in the VIP- but not in the PACAP-deficient mice. Baselines levels of FOS, p-MAPK or Per1 in the night were not altered by the loss of these peptides. In contrast, during the subjective day, light exposure increased the levels of FOS, p-MAPK and Per1 in the SCN of VIP-deficient mice, but not in the other genotypes. During this phase, baseline levels of these markers were reduced in the VIP-deficient mice compared with untreated controls. Finally, the loss of either neuropeptide reduced the magnitude of the light-evoked increase in Per1 levels in the adrenals in the subjective night without any change in baseline levels. In summary, our results indicate that both VIP and PACAP regulate the responsiveness of cells within the SCN to the effects of light. Furthermore, VIP, but not PACAP, is required for the appropriate temporal gating of light-induced gene expression within the SCN.