| Establishment of a depression model using dexamethasone-treated three-dimensional cultured rat cortical cells |
Mi Kyoung Seo  1,2, Sehoon Jeong 3, Woo Seok Cheon 4, Dong Yun Lee 2, Sumin Lee 5, Gyu-Hui Lee 2, Deok-Gyeong Kang 1, Dae-Hyun Seog 1,6,7, Seong-Ho Kim 2,8, Jung Goo Lee 2,4, Sung Woo Park 1,2,* |
| 1Department of Convergence Biomedical Science, College of Medicine, Inje University, Busan, Republic of Korea, 2Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea, 3Department of Artificial Intelligence and Data Science, Sejong University, Seoul, Republic of Korea, 4Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea, 5Institute for Digital Antiaging and Healthcare, Inje University, Gimhae, Republic of Korea, 6Department of Biochemistry, College of Medicine, Inje University, Busan, Republic of Korea, 7Dementia and Neurodegenerative Disease Research Center, College of Medicine, Inje University, Busan, Republic of Korea, 8Department of Internal Medicine, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea |
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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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| Accepted Manuscript [Submitted on 2025-01-09, Accepted on 2025-02-06] |
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