The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus

Authors

  • Joanna M. Dragich,

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    • *

      Present address: Department of Neurology, Columbia University, 650 West 168th Street, New York City, NY 10032, USA

  • Dawn H. Loh,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Louisa M. Wang,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Andrew M. Vosko,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Takashi Kudo,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Takahiro J. Nakamura,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Irene H. Odom,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Sei Tateyama,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Arkady Hagopian,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • James A. Waschek,

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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  • Christopher S. Colwell

    1. Department of Psychiatry and Biobehavioral Sciences, University of California – Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA
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Dr C. S. Colwell, as above.
E-mail: ccolwell@mednet.ucla.edu

Abstract

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.

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