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

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 mi-croglia activated by PM with an aerodynamic diameter <= 0.2 mu m (PM0.2). The activated-microglia induced A1s by se-creting interleukin-1 alpha, tumor necrosis factor-alpha, 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 indepen-dent 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 syn-aptic damage of neurons. This study indicates a potential approach for developing improved treatment of these dis-eases induced by particulate exposure. Synopsis: PM0.2-activated neuroinflammatory microglia induced A1 reactive astrocytes (A1s) by secreting IL-1 alpha, TNF-alpha, and C1q. PM0.2-induced A1s could promote synaptic damage of neuron by secreting complement 3.

Automated summary

Epidemiological studies have demonstrated that ambient fine particulate matter (PM) can lead to various neurodegenerative diseases, including Alzheimer's disease. This study reveals that PM with an aerodynamic diameter of <= 0.2 μm can induce the formation of A1 reactive astrocytes (A1s) through the activation of neuroinflammatory microglia. The A1s promote synaptic damage in neurons by secreting complement 3 (C3).