Analysis of mechanism of hierarchical rhythm and biological dock in mammals and avian species

通过免疫组织化学分析，我们在视交叉上核(SCN)中检测到一种肠脑肽，NMU，它是昼夜节律振荡器的主要部位。NMU基因表达呈昼夜节律性，高峰出现在SCN的CT4~8。两种NMU结合受体(NMU-R1和NMU-R2)也在SCN中表达，但两种受体的相角不同。侧脑室注射NMU可诱导SCN细胞Fos蛋白表达，并引起昼夜节律的相移。相移的大小具有剂量依赖性。这种NMU诱导的相移是非光学型的。RT-PCR分析显示即刻早期基因如c-fos、NGFI-A、NGFI-B和JunB在SCN中的表达增加。此外，侧脑室注射NMU可增加SCN内PER1的表达，但不增加PER2的表达。这些结果表明，NMU可能通过自分泌或旁分泌作用在SCN的昼夜节律振荡器中发挥重要作用。

By immunohistochemical analysis, we detected a gut-brain peptide, neuromedin U (NMU), in the suprachiasmatic nucleus (SCN) which is the site of master circadian oscillator. The NMU mRNA expressed circadian rhythm with the peak at CT4-8 in the SCN. The two NMU-binding receptors (NMU-R1 and NMU-R2) were also expressed in the SCN, but phase angles were different between both receptors. Intracerebroventricular injection (ICV) of NMU induced Fos protein in the SCN cells and caused a phase dependent phase shift of the circadian locomotor activity rhythm. The magnitude of phase shift was dose-dependent. This NMU-induced phase-shift was non-photic type. RT-PCR analyses revealed increases in the expression of immediate early genes, such as c-fos, NGFI-A, NGFI-B and JunB in SCN. Furthermore, ICV injection of NMU increased the expression of Per1, but not Per2 in the SCN. These results indicate that NMU may play some important role for circadian oscillator by autocrine or paracrine action in SCN.