A vascular endothelial cell, neuron, and microglia tri-culture model to study hypertension-related depression

作者：Hongxia Zhao, Lingge Huang, Jian Liu, Min Feng, Y. Liu, Hong Li, Shan Gong, Chun‐Ming Chen, Zeng Shuiqing, Ren Weiqiong · 发表于：Frontiers in Cellular Neuroscience · 年份：2025 · DOI：10.3389/fncel.2025.1553309 · 被引用次数：3 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Neuroinflammation and Neurodegeneration Mechanisms

Hypertension-related Depression (HD) is a complex mental disorder that exerts a significant negative impact on patients’ quality of life. Previous studies have demonstrated that damages to vascular endothelial and hippocampus are the primary pathological features in HD rats. Under hypertensive conditions, inflammatory cytokines in peripheral blood vessels can induce central nervous system inflammation through penetration of a damaged blood-brain barrier, peripheral immune cells, and neural pathways, damaging the brain and triggering HD. Therefore, interactions between vascular endothelial cells, neurons, and glial cells are critical for the understanding of HD. However, in vivo animal models are often limited by the complexity of intrinsic systems, high inter-individual variability, and stringent ethical regulations. A reliable model that could be easily manipulated is needed for investigating the mechanisms involved in communication between vascular endothelial cells, neurons, and glial cells in HD. We therefore aimed to create a composite tri-culture model consisting of rat aortic endothelial cells (RAECs), neurons, and microglia to study HD. First, RAECs were stimulated with lipopolysaccharide to mimic endothelial injury under hypertensive conditions. Vascular endothelial function and inflammatory levels were assessed using fluorescent probes and enzyme-linked immunosorbent assays. RAECs treated with 1 μg/ml LPS for 24 h had reduced levels of nitric oxide, increased levels...