Gastrin-releasing peptide mediates photic entrainable signals to dorsal subsets of suprachiasmatic nucleus via induction of Period gene in mice
Gastrin-releasing peptide mediates photic entrainable signals to dorsal subsets of suprachiasmatic nucleus via induction of Period gene in mice
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DOI：
10.1124/mol.61.1.26
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发表时间：
2002-01-01
影响因子：
3.6
通讯作者：
Shibata, S
中科院分区：
文献类型：
--
作者：
Aida, R;Moriya, T;Shibata, S
视交叉上核（SCN）是中枢生物钟的所在地，由两个神经元群组成（即，直接受光的腹侧SCN亚群和具有间接或弱光反应的自主振荡功能的背侧SCN亚群）。然而，光信号从腹侧到背侧SCN的传输机制尚不清楚。由于胃泌素释放肽（GRP），主要在腹侧SCN中表达，发挥相移作用，GRP受体的损失直观地意味着减少从腹侧到背侧SCN的光信息。因此，使用GRP受体缺陷小鼠，我们通过评估SCN中的行为节律和小鼠周期（mPer）基因的诱导来研究GRP和GRP受体参与光和GRP诱导的夹带，这被认为是光夹带的关键。在夜间给药GRP剂量依赖性产生的行为在野生型，但不是GRP受体缺陷型小鼠的相位延迟。GRP的这种相移与SCN背侧部分中mPer 1和mPer 2 mRNA以及c-Fos蛋白的诱导密切相关，在SCN背侧部分中GRP受体也大量表达。在GRP受体缺陷小鼠中，光诱导的行为相移以及背侧SCN中mPer mRNA和c-Fos蛋白的诱导均减弱。我们的研究表明，视网膜感受器腹侧区的SCN的GRP神经元通过mPer基因的诱导，将光信号从腹侧SCN传递到背侧SCN。
The suprachiasmatic nucleus (SCN), locus of the central circadian clock, consists of two neuronal populations (i.e., a light-recipient ventral SCN subpopulation directly entrained by light and a dorsal SCN subpopulation with an autonomous oscillatory function possessing an indirect or weak light response). However, the mechanism underlying the transmission of photic signals from the ventral to dorsal SCN remains unclear. Because gastrin-releasing peptide (GRP), expressed mainly in the ventral SCN, exerts phase-shifting actions, loss of the GRP receptor intuitively implies a reduction of photic information from the ventral to dorsal SCN. Therefore, using GRP receptor-deficient mice, we examined the involvement of GRP and the GRP receptor in light- and GRP-induced entrainment by the assessment of behavioral rhythm and induction of mouse-Period (mPer) gene in the SCN, which is believed to be a critical for photic entrainment. Administration of GRP during nighttime dose dependently produced a phase delay of behavior in wildtype but not GRP receptor-deficient mice. This phase-shift by GRP was closely associated with induction of mPer1 and mPer2 mRNA as well as c-Fos protein in the dorsal portion of the SCN, where the GRP receptor was also expressed abundantly. Both the light-induced phase shift in behavior and the induction of mPer mRNA and c-Fos protein in the dorsal SCN were attenuated in GRP receptor-deficient mice. Our present studies suggest that GRP neurons in the retinorecipient ventral area of the SCN convey the photic entrainable signals from the ventral SCN to the dorsal SCN via induction of the mPer gene.