The role of the neuropeptides PACAP and VIP in the photic regulation of gene expression in the suprachiasmatic nucleus.
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.
Dragich
Joanna M
JM
Department of Psychiatry and Biobehavioral Sciences, University of California - Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024 1759, USA.
Loh
Dawn H
DH
Wang
Louisa M
LM
Vosko
Andrew M
AM
Kudo
Takashi
T
Nakamura
Takahiro J
TJ
Odom
Irene H
IH
Tateyama
Sei
S
Hagopian
Arkady
A
Waschek
James A
JA
Colwell
Christopher S
CS
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D056950:Period Circadian Proteins / Q000096:biosynthesis / Q000235:genetics; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
C495402:Adcyap1 protein, mouse; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D016760:Proto-Oncogene Proteins c-fos; D014660:Vasoactive Intestinal Peptide; D020928:Mitogen-Activated Protein Kinases