2. Academic Validation
  3. The role of reactive astrocytes in neurotoxicity induced by ultrafine particulate matter

The role of reactive astrocytes in neurotoxicity induced by ultrafine particulate matter

  • Sci Total Environ. 2023 Jan 5;161416. doi: 10.1016/j.scitotenv.2023.161416.
Ben Li 1,  Xiaohan Chang 2,  Xiaomin Liang 2,  Ting Liu 2,  Yongmei Shen 2,  Qianwen Zhang 2,  Xiaohui Yang 3,  Yi Lyu 2,  Liangpo Liu 2,  Jianquan Guo 2,  Meiqiong Wu 2,  Yi Gao 2,  Xiaoyan Yan 2,  Tong Wang 2,  WenPing Zhang 2,  Yulan Qiu 2,  JinPing Zheng 4
Affiliations

Affiliations

  • 1 School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address: LBen@sxmu.edu.cn.
  • 2 School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.
  • 3 School of Materials Science and Engineering, Taiyuan University of Science and Technology, Shanxi, China.
  • 4 School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address: zheng_jp@sxmu.cn.
PMID: 36621481 DOI: 10.1016/j.scitotenv.2023.161416
Abstract

Epidemiological studies have shown that ambient fine particulate matter (PM) can cause various neurodegenerative diseases, including Alzheimer's disease. Reactive astrocytes are strongly induced by ambient fine PM, although their role is poorly understood. Herein, we show that A1 reactive astrocytes (A1s) were induced by neuroinflammatory microglia activated by PM with an aerodynamic diameter ≤ 0.2 μm (PM0.2). The activated-microglia induced A1s by secreting interleukin-1α, tumor necrosis factor-α, and complement 1q, and these cytokines acting together were necessary and sufficient to induce A1s. PM0.2-induced A1s could promote synaptic damage in neurons by secreting complement 3 (C3). SB 290157, a highly selective C3aR nonpeptide antagonist, partially ameliorated glial conditioned medium-induced synaptic injury. In vitro synaptic damage was partially prevented when A1 formation was blocked by minocycline. Finally, this study showed that N-acetyl-L-cysteine ameliorated PM0.2-induced neural damage independent of A1 differentiation. Collectively, these findings explain why central nervous system neurons suffer synaptic damage and neuroinflammation after PM0.2 exposure and suggest that this exposure induces A1s to contribute to synaptic damage of neurons. This study indicates a potential approach for developing improved treatment of these diseases induced by particulate exposure. SYNOPSIS: PM0.2-activated neuroinflammatory microglia induced A1 reactive astrocytes (A1s) by secreting IL-1α, TNF-α, and C1q. PM0.2-induced A1s could promote synaptic damage of neuron by secreting complement 3.

Keywords

Complement 3; PM(0.2); Reactive astrocytes; Synaptic damage.

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