Rhythmic expression of per1 in the dentate gyrus is suppressed by corticosterone: Implications for neurogenesis

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.

Research highlights▶ The rhythmic expression of per1 in the dentate gyrus was examined in per1-luciferase transgenic rats. ▶ Phasic expression was observed, 6 h out of phase with the plasma corticosterone rhythm but in phase with the suprachiasmatic nucleus (SCN). ▶ Per-1 rhythmic expression in the dentate gyrus, but not the SCN, was suppressed by clamping the daily corticosterone rhythm. ▶ These results relate to findings that a clamped corticosterone rhythm prevents fluoxetine (etc.) stimulating neurogenesis.