Mi Kyoung Seo, Sehoon Jeong, Woo Seok Cheon, Dong Yun Lee, Sumin Lee, Gyu-Hui Lee, Deok-Gyeong Kang, Dae-Hyun Seog, Seong-Ho Kim, Jung Goo Lee, Sung Woo Park
{"title":"地塞米松处理的三维培养大鼠皮质细胞抑郁模型的建立。","authors":"Mi Kyoung Seo, Sehoon Jeong, Woo Seok Cheon, Dong Yun Lee, Sumin Lee, Gyu-Hui Lee, Deok-Gyeong Kang, Dae-Hyun Seog, Seong-Ho Kim, Jung Goo Lee, Sung Woo Park","doi":"10.9758/cpn.25.1269","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong><i>In vitro</i> models are useful for exploring the molecular mechanisms underlying impaired neuroplasticity in depression. In this study, we developed a three-dimensional spheroid model in which we investigated the effects of the synthetic glucocorticoid dexamethasone on key pathways involved in neuroplasticity, specifically BDNF, sirtuin 1, and mTORC1 signaling.</p><p><strong>Methods: </strong>A micro-spheroid device was fabricated using photolithography and soft lithography, and cortical spheroids were generated from primary rat cortical cells. These spheroids, which contained neurons, astrocytes, microglia, and oligodendrocytes, were treated with various concentrations of dexamethasone.</p><p><strong>Results: </strong>Dexamethasone treatment (100, 200, and 300 μM) resulted in a dose-dependent reduction in cell viability, BDNF mRNA expression, and neurite outgrowth. At 100 μM, dexamethasone reduced the expression of BDNF and sirtuin 1 and decreased the phosphorylation of ERK1/2. It also decreased the phosphorylation of mTORC1, 4E-BP1, and p70S6K, as well as synaptic proteins such as PSD-95 and GluA1.</p><p><strong>Conclusion: </strong>Dexamethasone treatment inhibited pathways related to neuroplasticity. While dexamethasone-treated spheroids may serve as a basis for developing an <i>in vitro</i> model of depression, further validation is needed to confirm their broader applicability.</p>","PeriodicalId":10420,"journal":{"name":"Clinical Psychopharmacology and Neuroscience","volume":"23 3","pages":"418-432"},"PeriodicalIF":2.4000,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264662/pdf/","citationCount":"0","resultStr":"{\"title\":\"Establishment of a Depression Model Using Dexamethasone-treated Three-dimensional Cultured Rat Cortical Cells.\",\"authors\":\"Mi Kyoung Seo, Sehoon Jeong, Woo Seok Cheon, Dong Yun Lee, Sumin Lee, Gyu-Hui Lee, Deok-Gyeong Kang, Dae-Hyun Seog, Seong-Ho Kim, Jung Goo Lee, Sung Woo Park\",\"doi\":\"10.9758/cpn.25.1269\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong><i>In vitro</i> models are useful for exploring the molecular mechanisms underlying impaired neuroplasticity in depression. In this study, we developed a three-dimensional spheroid model in which we investigated the effects of the synthetic glucocorticoid dexamethasone on key pathways involved in neuroplasticity, specifically BDNF, sirtuin 1, and mTORC1 signaling.</p><p><strong>Methods: </strong>A micro-spheroid device was fabricated using photolithography and soft lithography, and cortical spheroids were generated from primary rat cortical cells. These spheroids, which contained neurons, astrocytes, microglia, and oligodendrocytes, were treated with various concentrations of dexamethasone.</p><p><strong>Results: </strong>Dexamethasone treatment (100, 200, and 300 μM) resulted in a dose-dependent reduction in cell viability, BDNF mRNA expression, and neurite outgrowth. At 100 μM, dexamethasone reduced the expression of BDNF and sirtuin 1 and decreased the phosphorylation of ERK1/2. It also decreased the phosphorylation of mTORC1, 4E-BP1, and p70S6K, as well as synaptic proteins such as PSD-95 and GluA1.</p><p><strong>Conclusion: </strong>Dexamethasone treatment inhibited pathways related to neuroplasticity. While dexamethasone-treated spheroids may serve as a basis for developing an <i>in vitro</i> model of depression, further validation is needed to confirm their broader applicability.</p>\",\"PeriodicalId\":10420,\"journal\":{\"name\":\"Clinical Psychopharmacology and Neuroscience\",\"volume\":\"23 3\",\"pages\":\"418-432\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264662/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Psychopharmacology and Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.9758/cpn.25.1269\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/3/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Psychopharmacology and Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.9758/cpn.25.1269","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Establishment of a Depression Model Using Dexamethasone-treated Three-dimensional Cultured Rat Cortical Cells.
Objective: In vitro models are useful for exploring the molecular mechanisms underlying impaired neuroplasticity in depression. In this study, we developed a three-dimensional spheroid model in which we investigated the effects of the synthetic glucocorticoid dexamethasone on key pathways involved in neuroplasticity, specifically BDNF, sirtuin 1, and mTORC1 signaling.
Methods: A micro-spheroid device was fabricated using photolithography and soft lithography, and cortical spheroids were generated from primary rat cortical cells. These spheroids, which contained neurons, astrocytes, microglia, and oligodendrocytes, were treated with various concentrations of dexamethasone.
Results: Dexamethasone treatment (100, 200, and 300 μM) resulted in a dose-dependent reduction in cell viability, BDNF mRNA expression, and neurite outgrowth. At 100 μM, dexamethasone reduced the expression of BDNF and sirtuin 1 and decreased the phosphorylation of ERK1/2. It also decreased the phosphorylation of mTORC1, 4E-BP1, and p70S6K, as well as synaptic proteins such as PSD-95 and GluA1.
Conclusion: Dexamethasone treatment inhibited pathways related to neuroplasticity. While dexamethasone-treated spheroids may serve as a basis for developing an in vitro model of depression, further validation is needed to confirm their broader applicability.
期刊介绍:
Clinical Psychopharmacology and Neuroscience (Clin Psychopharmacol Neurosci) launched in 2003, is the official journal of The Korean College of Neuropsychopharmacology (KCNP), and the associate journal for Asian College of Neuropsychopharmacology (AsCNP). This journal aims to publish evidence-based, scientifically written articles related to clinical and preclinical studies in the field of psychopharmacology and neuroscience. This journal intends to foster and encourage communications between psychiatrist, neuroscientist and all related experts in Asia as well as worldwide. It is published four times a year at the last day of February, May, August, and November.