The Kampo Medicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice
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 K...
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| creator | Tohyama, Masaya Takeda, Takashi Tanaka, Takashi Shimizu, Shoko Miyata, Shingo |
| description | 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. |
| doi_str_mv | 10.1155/2015/797280 |
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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.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2015/797280</identifier><identifier>PMID: 26106615</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Animals ; Behavior ; Blood-brain barrier ; Brain research ; Corticosteroids ; Corticosterone - blood ; Drugs, Chinese Herbal - administration & dosage ; Enzymes ; Folk medicine ; Gene expression ; Gene Expression Regulation - drug effects ; Genetic aspects ; Glucocorticoids - metabolism ; Health aspects ; Hypothalamo-Hypophyseal System - drug effects ; Hypothalamus ; Hypothalamus - drug effects ; Hypothalamus - metabolism ; Laboratory animals ; Medical research ; Medicine ; Medicine, Kampo - adverse effects ; Medicine, Primitive ; Mice ; MicroRNA ; MicroRNAs - biosynthesis ; MicroRNAs - genetics ; Observations ; Paraventricular Hypothalamic Nucleus - drug effects ; Pituitary-Adrenal System - drug effects ; Protein expression ; Proteins ; Rodents ; Serotonin ; Stress, Psychological - drug therapy ; Stress, Psychological - physiopathology ; Studies</subject><ispartof>BioMed research international, 2015-01, Vol.2015 (2015), p.1-8</ispartof><rights>Copyright © 2015 Shoko Shimizu et al.</rights><rights>COPYRIGHT 2015 John Wiley & Sons, Inc.</rights><rights>Copyright © 2015 Shoko Shimizu et al. Shoko Shimizu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2015 Shoko Shimizu et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-d6e5ae52198aa6d3427d59457ba430f705ecbfc878fdb32f50466da64a643533</citedby><cites>FETCH-LOGICAL-c491t-d6e5ae52198aa6d3427d59457ba430f705ecbfc878fdb32f50466da64a643533</cites><orcidid>0000-0001-8064-070X ; 0000-0003-2428-1946 ; 0000-0001-6524-3888</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461721/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461721/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26106615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tang, Yu-Ping</contributor><creatorcontrib>Tohyama, Masaya</creatorcontrib><creatorcontrib>Takeda, Takashi</creatorcontrib><creatorcontrib>Tanaka, Takashi</creatorcontrib><creatorcontrib>Shimizu, Shoko</creatorcontrib><creatorcontrib>Miyata, Shingo</creatorcontrib><title>The Kampo Medicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>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.</description><subject>Animals</subject><subject>Behavior</subject><subject>Blood-brain barrier</subject><subject>Brain research</subject><subject>Corticosteroids</subject><subject>Corticosterone - blood</subject><subject>Drugs, Chinese Herbal - administration & dosage</subject><subject>Enzymes</subject><subject>Folk medicine</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genetic aspects</subject><subject>Glucocorticoids - metabolism</subject><subject>Health aspects</subject><subject>Hypothalamo-Hypophyseal System - drug effects</subject><subject>Hypothalamus</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Laboratory animals</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine, Kampo - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tohyama, Masaya</au><au>Takeda, Takashi</au><au>Tanaka, Takashi</au><au>Shimizu, Shoko</au><au>Miyata, Shingo</au><au>Tang, Yu-Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Kampo Medicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>2015</volume><issue>2015</issue><spage>1</spage><epage>8</epage><pages>1-8</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><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.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>26106615</pmid><doi>10.1155/2015/797280</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-8064-070X</orcidid><orcidid>https://orcid.org/0000-0003-2428-1946</orcidid><orcidid>https://orcid.org/0000-0001-6524-3888</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Behavior Blood-brain barrier Brain research Corticosteroids Corticosterone - blood Drugs, Chinese Herbal - administration & dosage Enzymes Folk medicine Gene expression Gene Expression Regulation - drug effects Genetic aspects Glucocorticoids - metabolism Health aspects Hypothalamo-Hypophyseal System - drug effects Hypothalamus Hypothalamus - drug effects Hypothalamus - metabolism Laboratory animals Medical research Medicine Medicine, Kampo - adverse effects Medicine, Primitive Mice MicroRNA MicroRNAs - biosynthesis MicroRNAs - genetics Observations Paraventricular Hypothalamic Nucleus - drug effects Pituitary-Adrenal System - drug effects Protein expression Proteins Rodents Serotonin Stress, Psychological - drug therapy Stress, Psychological - physiopathology Studies |
| title | The Kampo Medicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice |
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