title: Serotonin modulates the suppressive effects of corticosterone on proliferating progenitor cells in the dentate gyrus of the hippocampus in the adult rat.
abstract: This series of experiments explores the interaction between corticosterone and serotonin (5-HT) in the regulation of cell proliferation in the dentate gyrus of the adult rat. Intracerebroventricular 5,7-DHT (5,7-dihydroxytryptamine) (either 200 or 300 microg) resulted in highly significant depletion of 5-HT as measured by high performance liquid chromatography in the frontal cortex but had no effect on the number of proliferating cells in the dentate gyrus by measuring 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 cytochemistry. Treatment with PCPA (p-chlorophenylalanine: a tryptophan hydroxylase inhibitor: 300 mg/kg initially followed by 100 mg/kg/day) resulted in reduced proliferation as measured by Ki-67 after 3 days treatment, but not by BrdU uptake, and not after 14 days treatment by either method. In addition, injection of corticosterone (10-40 mg/kg/day) for 8 days significantly reduced proliferation in the dentate gyrus, as expected, measured by both BrdU uptake and Ki-67 immunostaining. Adrenalectomized (ADX) rats with a replacement subcutaneous pellet of corticosterone showed reduced proliferation when given additional corticosterone (10 mg/kg/day for 8 days), but this was prevented by 5-HT depletion (i.c.v. 5,7-DHT). Finally, a dose-response study showed that progressive doses of corticosterone (0-40 mg/kg/day) in ADX rats resulted in diminished suppression of proliferation in 5-HT-depleted compared with 5-HT-intact rats. These results strongly suggest that 5-HT regulates the sensitivity of proliferating cells in the dentate gyrus to corticosterone.
authors.affiliation: Department of Anatomy, Cambridge Centre for Brain Repair, University of Cambridge, UK.
authors.forename: Guo-Jen
authors.initials: GJ
authors.lastname: Huang
authors.forename: Joe
authors.initials: J
authors.lastname: Herbert
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000315:Adrenalectomy; D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology* / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects*; D016707:Tissue Fixation
chemical_list: D000963:Antimetabolites; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D001973:Bromodeoxyuridine; D010134:Fenclonine; D003345:Corticosterone