Xu Yuhao, Wang Man, Wei Hong, Yu Ming, Li Yuefeng
Department of Radiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212001, China; Department of Neurology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China; Department of Neuroimaging Laboratory, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
Department of Radiology, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212001, China; Department of Neurology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, China.
Int Immunopharmacol. 2025 Jan 27;146:113946. doi: 10.1016/j.intimp.2024.113946. Epub 2024 Dec 29.
Depression is a prevalent mental illness that significantly impairs individuals' overall quality of life and physical well-being. However, the pathological mechanisms of depression remain unclear, and effective treatment strategies are urgently needed. Pentraxin 3 (PTX3), a long pentraxin protein, plays a significant role in various pathological conditions, including infections, immune responses, and tissue repair. In this study, we collected serum from patients with depression and established both animal and cell models of depression. We found that PTX3 expression was significantly reduced in both the serum of patients with depression and the hippocampus of chronic unpredictable mild stress (CUMS) mice. PTX3 supplementation markedly improved depressive-like behavior in CUMS mice and promoted microglial M2 polarization. In the LPS-induced BV2 cell model, PTX3 overexpression facilitated microglial M2 polarization via activation of the CREB/CEBPb axis. Additionally, PTX3 enhanced fibroblast growth factor 22 (FGF22) expression and excitatory synapse formation in the CA3 region of the hippocampus in CUMS mice. In the dexamethasone (DXM)-treated SH-SY5Y cell model, PTX3 overexpression increased SPI1 expression, elevated FGF22 transcriptional activity, and promoted the expression of excitatory synapse-related proteins PSD95 and VGLUT1. In summary, our study demonstrates that PTX3 promotes microglial M2 polarization and excitatory synapse formation in the hippocampus, suggesting potential antidepressant effects and providing theoretical support for considering PTX3 as a therapeutic target for depression.
抑郁症是一种常见的精神疾病，严重损害个体的整体生活质量和身体健康。然而，抑郁症的病理机制仍不清楚，迫切需要有效的治疗策略。五聚体蛋白3（PTX3）是一种长链五聚体蛋白，在包括感染、免疫反应和组织修复在内的各种病理状况中发挥重要作用。在本研究中，我们收集了抑郁症患者的血清，并建立了抑郁症的动物和细胞模型。我们发现，抑郁症患者血清和慢性不可预测轻度应激（CUMS）小鼠海马体中的PTX3表达均显著降低。补充PTX3可显著改善CUMS小鼠的抑郁样行为，并促进小胶质细胞M2极化。在脂多糖（LPS）诱导的BV2细胞模型中，PTX3过表达通过激活CREB/CEBPb轴促进小胶质细胞M2极化。此外，PTX3增强了CUMS小鼠海马体CA3区成纤维细胞生长因子22（FGF22）的表达和兴奋性突触形成。在用地塞米松（DXM）处理的SH-SY5Y细胞模型中，PTX3过表达增加了SPI1的表达，提高了FGF22的转录活性，并促进了兴奋性突触相关蛋白PSD95和VGLUT1的表达。总之，我们的研究表明，PTX3促进海马体中小胶质细胞M2极化和兴奋性突触形成，提示其潜在的抗抑郁作用，并为将PTX3作为抑郁症的治疗靶点提供了理论支持。
