中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3238-3248.doi: 10.4103/NRR.NRR-D-24-01469

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

破坏Nrf2-介导的星形胶质细胞与小胶质细胞之间的通讯：空气污染导致抑郁与胶质细胞互作新机制

  

  • 出版日期:2026-07-15 发布日期:2026-04-01
  • 基金资助:
    该研究获得科技部重点研发项目 (2023YFC3708303)，国家自然科学基金面上项目（82241084）以及北京市高层次公共卫生技术人才（学科带头人-03-29）项目的支持。

Long-term real-world PM2.5 exposure induces depression-like behaviors in mice by disrupting nuclear factor erythroid 2-related factor 2-mediated astrocyte-to-microglia communication 

Nannan Huang1, Weiqing Shi2, Cuishuang Dong1, Bin Li1, Yaohan Wang1, Hanqing Chen1, 3, *, Xiaobo Li1, *   

  1. 1School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University, Beijing, China; 
    2Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, China; 
    3Department of Nutrition & Food Hygiene, School of Public Health, Capital Medical University, Beijing, China
  • Online:2026-07-15 Published:2026-04-01
  • Contact: Xiaobo Li, PhD, MD, xiaoboli@ccmu.edu.cn; Hanqing Chen, PhD, chenhq@ccmu.edu.cn.
  • Supported by:
    This work was supported by the National Basic Research Plan Project of China, No. 2023YFC3708303; the National Natural Science Foundation of China, No. 82241084; the High-level Talent in Public Health of Beijing, No. Discipline Leaders-03-29 (all to XL).

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摘要：

长期暴露于环境中的细颗粒物（PM2.5）会增加人类神经中毒的风险。然而，有关慢性 PM2.5 诱发抑郁样行为的内在机制和潜在治疗策略的研究仍然很少。实验首先通过构建长达15周的真实世界PM2.5实验动物暴露模型，发现暴露组小鼠出现抑郁样行为，同时伴随着脑组织中氧化应激反应加重，星形胶质细胞异常活化。以此为基础，通过构建双侧和单侧星形胶质细胞特异性的Nrf2敲低（KD）小鼠模型，证实星形胶质细胞与小胶质细胞之间的通讯因星形胶质细胞中Nrf2缺失而受到干扰。当抑制星形胶质细胞Nrf2表达，小胶质细胞的吞噬能力随之被减弱，最终加重了小鼠的抑郁样行为。从健康干预的角度出发，实验筛选了3种具有抗氧化作用的植物化学物，发现原花青素能够通过靶向激活星形胶质细胞的Nrf2信号通路，恢复氧化还原稳态，改善PM2.5暴露所引起的抑郁样行为，并减少神经元损伤。以上研究提示膳食补充原花青素可能是预防空气污染所致神经损伤的一种有效干预手段。


https://orcid.org/0009-0006-4349-2473 (Xiaobo Li); https://orcid.org/0000-0001-5442-2071 (Hanqing Chen)

关键词: 空气污染, 星形胶质细胞与小胶质细胞间的通讯, 抑郁样行为, 细颗粒物（PM2.5）, 神经毒性, Nrf2, 氧化应激, 原花青素

Abstract: Long-term exposure to ambient fine particulate matter (PM2.5) may increase the risk of neurotoxicity in human populations. However, research studies on the underlying mechanisms of chronic PM2.5-induced depression-like behaviors, and potential therapeutical strategies, remain scarce. In the present study, after long-term exposure to real-world PM2.5 for 15 weeks, male mice displayed depression-like behaviors, which were revealed using the open field and sucrose preference tests. Mechanistically, chronic PM2.5 exposure promoted astrocytic A1 polarization and disrupted reduction–oxidation balance in the mouse hippocampus. Furthermore, PM2.5-exposed mice displayed pathological damage to hippocampal neurons as well as the inhibition of nuclear factor erythroid 2-related factor 2 signaling. Astrocytic ablation of nuclear factor erythroid 2-related factor 2 exacerbated PM2.5-induced hippocampal neuronal injury in mice via the disruption of astrocyte-to-microglia communication; this finding was confirmed in mice with bilateral and unilateral hippocampal astrocytic Nfe2l2 knockdown. Importantly, the upregulation of nuclear factor erythroid 2-related factor 2 activation by procyanidin significantly ameliorated PM2.5-induced depression-like behaviors through the remodeling of astrocyte-to-microglia communication. Together, our findings shed light on the important role of hippocampal astrocytic nuclear factor erythroid 2-related factor 2 activation for maintaining astrocyte-to-microglia communication, and indicate potential research avenues for therapeutic strategies against PM2.5-induced depresson-like behaviors. 

Key words: air pollution, astrocyte-to-microglia communication, depression-like behaviors, fine particulate matter (PM2.5), neurotoxicity, nuclear factor erythroid 2-related factor 2, oxidative stress, procyanidins