Autophagy alleviates hippocampal neuroinflammation by inhibiting the NLRP3 inflammasome in a juvenile rat model exposed particulate matter.

Abstract

Ambient fine particulate matter (PM) is a global public and environmental problem. PM is closely associated with several neurological diseases, which typically involve neuroinflammation. We investigated the impact of PM exposure on neuroinflammation using both in vivo (in a juvenile rat model with PM exposure concentrations of 1, 2, and 10 mg/kg for 28 days) and in vitro (in BV-2 and HT-22 cell models with PM concentrations of 50-200 μg/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leading to the production of IL-1β and IL-18 in the rat hippocampus and BV-2 cells. Furthermore, inhibition of the NLRP3 inflammasome with MCC950 effectively reduced neuroinflammation and ameliorated hippocampal damage. In addition, autophagy activation was observed in the hippocampus of PM-exposed rats, and the promotion of autophagy by rapamycin (Rapa) effectively attenuated the NLRP3-mediated neuroinflammation induced by PM exposure. However, autophagic flow was blocked in BV-2 cells exposed to PM, and Rapa failed to ameliorate NLRP3 inflammasome activation. We found that autophagy was activated in HT-22 cells exposed to PM and that treatment with Rapa reduced the release of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as cell apoptosis. In a subsequent coculture model of BV-2 and HT-22 cells, we observed the activation of the NLRP3 inflammasome in BV-2 cells when the HT-22 cells were exposed to PM, and this activation was alleviated when PM-exposed HT-22 cells were pretreated with Rapa. Overall, our study revealed that PM exposure triggered hippocampal neuroinflammation by activating the NLRP3 inflammasome. Notably, autophagy mitigated NLRP3 inflammasome activation, potentially by reducing neuronal ROS and apoptosis. This research emphasized the importance of reducing PM exposure and provided valuable insight into its neurotoxicity.

• Authors: Jianxiong Gui, Jie Liu, Lingman Wang, Xiaoyue Yang, Bing Tian, Hanyu Luo, Dishu Huang, Ziyao Han, Jiaxin Yang, Ran Ding, Zhixu Fang, Xue Li, Li Cheng, Li Jiang
• Journal: Toxicology (Toxicology) Vol. 502 Pg. 153730 (02 2024) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 38237716 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier B.V. All rights reserved.

Chemical References

• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Reactive Oxygen Species
• Particulate Matter

Topics

• Rats
• Animals
• Inflammasomes (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Reactive Oxygen Species
• Neuroinflammatory Diseases
• Particulate Matter (toxicity)
• Autophagy
• Hippocampus (metabolism)