{"title":"丹参素干预通过激活雷帕霉素信号和脑源性神经营养因子释放的哺乳动物靶点介导快速抗抑郁作用。","authors":"Han-Wen Chuang, Chih-Chia Huang, Kuang-Ti Chen, Yen-Yu Kuo, Jou-Hua Ren, Tse-Yen Wang, Mang-Hung Tsai, Po-Ting Chen, I-Hua Wei","doi":"10.30773/pi.2024.0238","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.</p><p><strong>Methods: </strong>Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK-mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.</p><p><strong>Results: </strong>Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK-mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.</p><p><strong>Conclusion: </strong>Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR-mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.</p>","PeriodicalId":21164,"journal":{"name":"Psychiatry Investigation","volume":"21 11","pages":"1286-1298"},"PeriodicalIF":1.8000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611467/pdf/","citationCount":"0","resultStr":"{\"title\":\"Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release.\",\"authors\":\"Han-Wen Chuang, Chih-Chia Huang, Kuang-Ti Chen, Yen-Yu Kuo, Jou-Hua Ren, Tse-Yen Wang, Mang-Hung Tsai, Po-Ting Chen, I-Hua Wei\",\"doi\":\"10.30773/pi.2024.0238\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.</p><p><strong>Methods: </strong>Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK-mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.</p><p><strong>Results: </strong>Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK-mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.</p><p><strong>Conclusion: </strong>Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR-mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.</p>\",\"PeriodicalId\":21164,\"journal\":{\"name\":\"Psychiatry Investigation\",\"volume\":\"21 11\",\"pages\":\"1286-1298\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611467/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychiatry Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.30773/pi.2024.0238\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychiatry Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.30773/pi.2024.0238","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/18 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release.
Objective: Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study.
Methods: Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK-mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu.
Results: Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK-mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site.
Conclusion: Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR-mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.
期刊介绍：
The Psychiatry Investigation is published on the 25th day of every month in English by the Korean Neuropsychiatric Association (KNPA). The Journal covers the whole range of psychiatry and neuroscience. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and management of neuropsychiatric disorders and symptoms, as well as researches related to cross cultural psychiatry and ethnic issues in psychiatry. The Journal publishes editorials, review articles, original articles, brief reports, viewpoints and correspondences. All research articles are peer reviewed. Contributions are accepted for publication on the condition that their substance has not been published or submitted for publication elsewhere. Authors submitting papers to the Journal (serially or otherwise) with a common theme or using data derived from the same sample (or a subset thereof) must send details of all relevant previous publications and simultaneous submissions. The Journal is not responsible for statements made by contributors. Material in the Journal does not necessarily reflect the views of the Editor or of the KNPA. Manuscripts accepted for publication are copy-edited to improve readability and to ensure conformity with house style.
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