Scholarlink

<p>Three-dimensional (3D) <i>in vitro</i> models of depression are valuable platforms for investigating disease pathophysiology, elucidating the mechanisms of antidepressant action, assessing drug efficacy, and facilitating the development of novel therapeutics. In our previous study, 3D cortical spheroids exposed to the synthetic glucocorticoid dexamethasone exhibited marked impairments in neuroplasticity, representing a key pathological feature of depression. The present study aimed to evaluate the applicability of this model under escitalopram treatment and to elucidate the molecular mechanisms involved. Primary rat cortical cell-derived 3D spheroids were exposed to dexamethasone (100 µM) and subsequently treated with escitalopram at concentrations of 0.1, 1, and 10 µM. Western blot analysis was performed to measure brain-derived neurotrophic factor (BDNF), mTORC1–related signaling proteins, and synaptic proteins including PSD-95 and GluA1. Neurite outgrowth was visualized via immunofluorescence and quantified using Sholl analysis. Dexamethasone significantly reduced BDNF expression, neurite complexity, and phosphorylation of mTORC1, 4E-BP1, and p70S6K, along with decreasing synaptic protein levels. Escitalopram dose–dependently reversed these deficits, with the most pronounced effects observed at 10 µM. These findings demonstrate that escitalopram is associated with enhanced neuroplasticity and increased activation of mTORC1 signaling in dexamethasone-treated cortical spheroids, validating this system as a 3D <i>in vitro</i> for mechanistic investigation of stress-related neuroplasticity impairment.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dexamethasone-induced 3D cortical spheroid model of stress-related neuroplasticity impairment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月9日

查看全文
  • Mi Kyoung Seo,
  • Jung Goo Lee,
  • Jung An Lee,
  • Ji Won Park,
  • Deok-Gyeong Kang,
  • Dae-Hyun Seog,
  • Myoung Hun Kim,
  • Sehoon Jeong,
  • Sung Woo Park

摘要

Three-dimensional (3D) in vitro models of depression are valuable platforms for investigating disease pathophysiology, elucidating the mechanisms of antidepressant action, assessing drug efficacy, and facilitating the development of novel therapeutics. In our previous study, 3D cortical spheroids exposed to the synthetic glucocorticoid dexamethasone exhibited marked impairments in neuroplasticity, representing a key pathological feature of depression. The present study aimed to evaluate the applicability of this model under escitalopram treatment and to elucidate the molecular mechanisms involved. Primary rat cortical cell-derived 3D spheroids were exposed to dexamethasone (100 µM) and subsequently treated with escitalopram at concentrations of 0.1, 1, and 10 µM. Western blot analysis was performed to measure brain-derived neurotrophic factor (BDNF), mTORC1–related signaling proteins, and synaptic proteins including PSD-95 and GluA1. Neurite outgrowth was visualized via immunofluorescence and quantified using Sholl analysis. Dexamethasone significantly reduced BDNF expression, neurite complexity, and phosphorylation of mTORC1, 4E-BP1, and p70S6K, along with decreasing synaptic protein levels. Escitalopram dose–dependently reversed these deficits, with the most pronounced effects observed at 10 µM. These findings demonstrate that escitalopram is associated with enhanced neuroplasticity and increased activation of mTORC1 signaling in dexamethasone-treated cortical spheroids, validating this system as a 3D in vitro for mechanistic investigation of stress-related neuroplasticity impairment.