title: The Kampo Medicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice.
abstract: It is well known that glucocorticoid receptor (GR) signaling regulates the hypothalamic-pituitary-adrenal (HPA) axis, and GR expression level is associated with HPA axis activity. Recent studies revealed that microRNA- (miR-) 18 and/or 124a are candidate negative regulators of GR in the brain. The Kampo medicine Yokukansan (YKS) can affect psychological symptoms such as depression and anxiety that are associated with stress responses. In this study, we evaluated the effect of YKS on miR-18 and 124a and GR levels in mice exposed to stress. We found that YKS pretreatment normalized elevated plasma corticosterone levels in stress-exposed mice. In addition, GR mRNA levels were downregulated in the brain following stress exposure. While miR-124a expression levels were not altered in the hypothalamus of stress-exposed mice, miR-18 levels decreased in the hypothalamus of YKS-pretreated mice after stress exposure. Finally, GR protein levels in the paraventricular nucleus (PVN) of the hypothalamus after stress exposure recovered in YKS-pretreated mice. Collectively, these data suggest that YKS normalizes GR protein levels by regulating miR-18 expression in the hypothalamus, thus normalizing HPA axis activity following stress exposure.
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Shoko
authors.identifier: 0000-0001-6524-3888
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Women Medicine, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Takashi
authors.identifier: 0000-0003-2428-1946
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan ; Osaka Prefectural Hospital Organization, Osaka 558-8558, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.affiliation: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Shingo
authors.identifier: 0000-0001-8064-070X
authors.initials: S
authors.lastname: Miyata
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D020835:Medicine, Kampo / Q000009:adverse effects*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D004365:Drugs, Chinese Herbal; D005938:Glucocorticoids; C552691:MIRN18 microRNA, mouse; D035683:MicroRNAs; C524644:Yi-Gan San; D003345:Corticosterone