title: Yokukansan normalizes glucocorticoid receptor protein expression in oligodendrocytes of the corpus callosum by regulating microRNA-124a expression after stress exposure.
abstract: Stressful events are known to down-regulate expression levels of glucocorticoid receptors (GRs) in the brain. Recently, we reported that stressed mice with elevated plasma levels of corticosterone exhibit morphological changes in the oligodendrocytes of nerve fiber bundles, such as those in the corpus callosum. However, little is known about the molecular mechanism of GR expression regulation in oligodendrocytes after stress exposure. A previous report has suggested that GR protein levels might be regulated by microRNA (miR)-18 and/or -124a in the brain. In this study, we aimed to elucidate the GR regulation mechanism in oligodendrocytes and evaluate the effects of yokukansan (YKS), a Kampo medicine, on GR protein regulation. Acute exposure to stress increased plasma corticosterone levels, decreased GR protein expression, and increased miR-124a expression in the corpus callosum of adult male mice, though the GR mRNA and miR-18 expression levels were not significant changes. YKS normalized the stress-induced changes in the plasma corticosterone, GR protein, and miR124a expression levels. An oligodendrocyte primary culture study also showed that YKS down-regulated miR-124a, but not miR-18, expression levels in dexamethasone-treated cells. These results suggest that the down-regulation of miR124a expression might be involved in the normalization of stress-induced decreases in GR protein in oligodendrocytes by YKS. This effect may imply the molecular mechanisms underlying the ameliorative effects of YKS on psychological symptoms and stress-related behaviors.
authors: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors: Shoko
authors: S
authors: Shimizu
authors: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan.
authors: Takashi
authors: T
authors: Tanaka
authors: 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: Masaya
authors: M
authors: Tohyama
authors: Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kinki University, Osaka-sayama, Osaka 589-8511, Japan. Electronic address: smiyata@med.kindai.ac.jp.
authors: Shingo
authors: S
authors: Miyata
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003337:Corpus Callosum / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D004365:Drugs, Chinese Herbal; D005938:Glucocorticoids; C548144:MIRN124 microRNA, rat; C552691:MIRN18 microRNA, mouse; C000604346:MIRN18 microRNA, rat; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C524644:Yi-Gan San; D003907:Dexamethasone; D003345:Corticosterone
keywords: Corpus callosum; Glucocorticoid receptor; HPA axis; Stress responses; Yokukansan; microRNA