Department of Physiology, Development and Neuroscience, University of Cambridge, UK.
Neurosci Lett. 2011 Feb 11;489(3):177-81. doi: 10.1016/j.neulet.2010.12.011. Epub 2010 Dec 14.
The stimulating action of anti-depressant drugs on the number of mitotic cells on the dentate gyrus on the adult rat depends on an intact diurnal rhythm of corticosterone. This suggests that there may be a clock mechanism in the dentate gyrus which is sensitive to corticoids. This paper reports the diurnal expression the 'clock' gene per1 in the dentate gyrus, and how it is altered by clamping the diurnal rhythm in corticosterone. We show that there is a diurnal rhythm in the number of mitotic progenitor cells in the dentate gyrus of the hippocampus in adult male per1-luciferase rats, approximately 6 h out of phase with the plasma corticosterone rhythm. This is suppressed by clamping the daily corticosterone levels by a subcutaneous implant of corticosterone (100 mg). There was also a daily rhythm of per1 expression in both suprachiasmatic nucleus (SCN) and the dentate gyrus, which were in phase with one another. The per1 rhythm in the dentate gyrus, but not the SCN, was suppressed by clamping the plasma corticosterone rhythm. These results are related to the previous finding that clamping the corticosterone rhythm also prevents the stimulating action of fluoxetine and other controlling agents on the mitotic activity of the progenitor cells.
抗抑郁药对成年大鼠齿状回有丝分裂细胞数量的刺激作用取决于皮质酮昼夜节律的完整。这表明齿状回中可能存在对皮质酮敏感的时钟机制。本文报告了齿状回“时钟”基因 per1 的昼夜表达，以及昼夜皮质酮节律对其的改变。我们发现，成年雄性 per1-荧光素酶大鼠海马齿状回的有丝分裂祖细胞数量存在昼夜节律，大约与血浆皮质酮节律相差 6 小时。通过皮下植入皮质酮（100mg）来控制每日皮质酮水平可抑制这种节律。在视交叉上核（SCN）和齿状回中也存在 per1 表达的昼夜节律，它们彼此同步。齿状回中的 per1 节律，但 SCN 中的 per1 节律不受血浆皮质酮节律的抑制。这些结果与先前的发现有关，即抑制皮质酮节律也会阻止氟西汀和其他调控因子对祖细胞有丝分裂活性的刺激作用。
