Lipocalin-type prostaglandin D synthase regulates light-induced phase advance of the central circadian rhythm in mice

Commun Biol. 2020 Oct 8;3(1):557. doi: 10.1038/s42003-020-01281-w.

Abstract

We previously showed that mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit attenuated light-induced phase shift. To explore the underlying mechanisms, we performed gene expression analysis of laser capture microdissected suprachiasmatic nuclei (SCNs) and found that lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is involved in the impaired response to light stimulation in the late subjective night in PACAP-deficient mice. L-PGDS-deficient mice also showed impaired light-induced phase advance, but normal phase delay and nonvisual light responses. Then, we examined the receptors involved in the response and observed that mice deficient for type 2 PGD2 receptor DP2/CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cells) show impaired light-induced phase advance. Concordant results were observed using the selective DP2/CRTH2 antagonist CAY10471. These results indicate that L-PGDS is involved in a mechanism of light-induced phase advance via DP2/CRTH2 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Circadian Rhythm / radiation effects
  • Genes / genetics
  • Genes / physiology
  • In Situ Hybridization
  • Intramolecular Oxidoreductases / metabolism
  • Intramolecular Oxidoreductases / physiology*
  • Light
  • Lipocalins / metabolism
  • Lipocalins / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
  • Pituitary Adenylate Cyclase-Activating Polypeptide / physiology
  • Suprachiasmatic Nucleus / metabolism

Substances

  • Adcyap1 protein, mouse
  • Lipocalins
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase