title: Antidepressant-like effects of Cortex Mori Radicis extract via bidirectional phosphorylation of glucocorticoid receptors in the hippocampus.
abstract: Excessive and prolonged secretion of adrenal glucocorticoids leads to a wide range of pathophysiological processes, including depression. Glucocorticoids, which act at glucocorticoid receptors (GR), are key regulators of the limbic hypothalamic-pituitary-adrenocortical (HPA) axis. In the present study, the antidepressant-like effects of the alcohol extract Cortex Mori Radicis (CMR) and its role in GR signalling were investigated. Male Wistar rats were administered CMR extract (50, 100, 200mg/kg, p.o.) daily for 5 days and then exposed to the forced swim test (FST). Behavioural analyses showed that CMR extract dose-dependently decreased immobility time during forced swimming. CMR extract also decreased the limbic HPA axis response to the FST, as indicated by an attenuated corticosterone response and decreased c-fos immunoreactivity in the dentate gyrus. Reduced hippocampal GR expression following exposure to the FST was reversed by CMR treatment. Moreover, a prominent increase in GR phosphorylation at S232 and a decrease at S246 were noted following treatment with CMR. This resulted in a high pGR(S232)/(S246) ratio. CMR treatment also produced a downregulation of serine/threonine protein phosphatase 5 levels, producing a strong negative relationship with pGR(S232). Taken together, our findings suggest that the alcohol extract CMR promotes antidepressant-like effects through bidirectional phosphorylation of GR at S232 and S246.
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea.
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea.
authors.forename: Wan-Soon
authors.initials: WS
authors.lastname: Park
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea.
authors.forename: Young Han
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea.
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Functional Food Resources Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Functional Food Resources Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors.forename: Daeseok
authors.initials: D
authors.lastname: Han
authors.affiliation: Laboratory of Neuropharmacology, Department of Nursing, Shikoku University, School of Health Sciences, Tokushima, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Morita
authors.affiliation: Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Republic of Korea. Electronic address: swher@kbsi.re.kr.
authors.forename: Song
authors.initials: S
authors.lastname: Her
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003345:Corticosterone / Q000378:metabolism; D019417:Hindlimb Suspension / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D031625:Morus / Q000737:chemistry*; D009043:Motor Activity / Q000187:drug effects; D009687:Nuclear Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D006727:Hormone Antagonists; D009687:Nuclear Proteins; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5; D003345:Corticosterone