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

作者全名："Gui, Jianxiong; Liu, Jie; Wang, Lingman; Yang, Xiaoyue; Tian, Bing; Luo, Hanyu; Huang, Dishu; Han, Ziyao; Yang, Jiaxin; Ding, Ran; Fang, Zhixu; Li, Xue; Cheng, Li; Jiang, Li"

作者地址："[Gui, Jianxiong; Liu, Jie; Wang, Lingman; Yang, Xiaoyue; Tian, Bing; Luo, Hanyu; Huang, Dishu; Han, Ziyao; Yang, Jiaxin; Ding, Ran; Fang, Zhixu; Li, Xue; Cheng, Li; Jiang, Li] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Dept Neurol,Childrens Hosp,Chongqing Key Lab Child, Chongqing 400014, Peoples R China; [Jiang, Li] Chongqing Med Univ, Dept Neurol, Childrens Hosp, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China"

通信作者："Jiang, L (通讯作者)，Chongqing Med Univ, Dept Neurol, Childrens Hosp, 136 Zhongshan Er Rd, Chongqing 400014, Peoples R China."

来源：TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001166205700001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：502

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Particulate matter; Neuroinflammation; NLRP3 inflammasome; Autophagy

摘要："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 mu g/ml for 24 h). We observed that PM exposure induced the activation of the NLRP3 inflammasome, leading to the production of IL-1 beta 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."

基金机构：National Natural Science Foundation of China [82301338]; China Postdoctoral Science Foundation [2022M710553]; Chongqing Post- doctoral Science Foundation [CSTB2022NSCQ- BHX0708]

基金资助正文：This work was supported by the National Natural Science Foundation of China [grant number 82301338] ; the China Postdoctoral Science Foundation [grant number 2022M710553] ; and the Chongqing Post- doctoral Science Foundation [grant number CSTB2022NSCQ- BHX0708] .