Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Commun Biol. 2020 Oct 8;3(1):557. doi: 10.1038/s42003-020-01281-w.
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 PGD 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.
我们之前的研究表明，缺乏垂体腺苷酸环化酶激活肽（PACAP）的小鼠表现出光诱导相位偏移减弱。为了探索潜在的机制，我们对激光捕获微解剖视交叉上核（SCN）进行了基因表达分析，发现亲脂素型前列腺素（PG）D 合酶（L-PGDS）参与了 PACAP 缺乏小鼠在晚主观夜间对光刺激反应受损。L-PGDS 缺乏的小鼠也表现出光诱导相位提前受损，但正常的相位延迟和非视觉光反应。然后，我们检查了参与反应的受体，并观察到缺乏 2 型 PGD 受体 DP2/CRTH2（Th2 细胞表达的趋化因子受体同源物）的小鼠表现出光诱导相位提前受损。使用选择性 DP2/CRTH2 拮抗剂 CAY10471 观察到了一致的结果。这些结果表明，L-PGDS 通过 DP2/CRTH2 信号参与了光诱导相位提前的机制。
