Establishment of a Depression Model Using Dexamethasone-treated Three-dimensional Cultured Rat Cortical Cells.

IF 2.4 4区医学 Q3 NEUROSCIENCES

Clinical Psychopharmacology and Neuroscience Pub Date : 2025-08-31 Epub Date: 2025-03-10 DOI:10.9758/cpn.25.1269

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

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引用次数: 0

Abstract

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.

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地塞米松处理的三维培养大鼠皮质细胞抑郁模型的建立。

目的：通过体外模型探讨抑郁症神经可塑性受损的分子机制。在这项研究中，我们建立了一个三维球体模型，研究了合成糖皮质激素地塞米松对神经可塑性关键通路的影响，特别是BDNF、sirtuin 1和mTORC1信号通路。方法：采用光刻法和软光刻法制备微球体装置，用原代大鼠皮质细胞制备皮质球体。这些含有神经元、星形胶质细胞、小胶质细胞和少突胶质细胞的球体用不同浓度的地塞米松处理。结果：地塞米松治疗（100、200和300 μM）导致细胞活力、BDNF mRNA表达和神经突起生长呈剂量依赖性降低。在100 μM时，地塞米松降低BDNF和sirtuin 1的表达，降低ERK1/2的磷酸化。它还降低了mTORC1、4E-BP1和p70S6K以及PSD-95和GluA1等突触蛋白的磷酸化。结论：地塞米松治疗可抑制神经可塑性相关通路。虽然地塞米松治疗的球体可以作为开发抑郁症体外模型的基础，但需要进一步验证以确认其更广泛的适用性。

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来源期刊

Clinical Psychopharmacology and Neuroscience NEUROSCIENCESPHARMACOLOGY & PHARMACY-PHARMACOLOGY & PHARMACY

CiteScore

4.70

自引率

12.50%

发文量

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.