Zinc Oxide Nanoparticles Exacerbate Epileptic Seizures by Modulating the TLR4-Autophagy Axis

作者全名："Ke, Pingyang; Liu, Jing; Chen, Chengzhi; Luo, Sen; Gu, Huiwen; Gu, Juan; Liu, Yan; Ma, Yuanlin; Meng, Yuan; Hu, Liqin; Tian, Xin; Xiao, Fei"

作者地址："[Ke, Pingyang; Liu, Jing; Liu, Yan; Ma, Yuanlin; Meng, Yuan; Hu, Liqin; Tian, Xin; Xiao, Fei] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing Key Lab Neurol, Chongqing, Peoples R China; [Liu, Jing] Chongqing Univ Three Gorges Hosp, Dept Neurol, Chongqing, Peoples R China; [Chen, Chengzhi; Luo, Sen; Gu, Huiwen] Chongqing Med Univ, Sch Publ Hlth & Management, Dept Occupat & Environm Hlth, Chongqing, Peoples R China; [Gu, Juan] Southwest Med Univ, Inst Cardiovasc Res, Key Lab Med Electrophysiol, Minist Educ, Luzhou, Sichuan, Peoples R China; [Gu, Juan] Southwest Med Univ, Inst Cardiovasc Res, Med Electrophysiol Key Lab Sichuan Prov, Luzhou, Sichuan, Peoples R China"

通信作者："Tian, X; Xiao, F (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing Key Lab Neurol, Chongqing, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001177680600001

JCR分区：Q1

影响因子：6.6

年份：2024

卷号：19

期号：　

开始页：2025

结束页：2038

文献类型：Article

关键词：zinc oxide nanoparticles; epilepsy; excitation/inhibition balance; autophage

摘要："Background: Zinc oxide nanoparticles (ZnO NPs) has been widely used in various fields and has had an important impact on human public health. In addition, it inevitably damages human health, including neurological diseases. Therefore, this study explored the effect of ZnO NPs on epilepsy. Methods: The effect of ZnO NPs on epilepsy was observed by behavioral analysis. TLR4 expression and autophagy related pathways were detected by RNA-seq and Western blot. In addition, the cell types of autophagy were detected by immunofluorescence. Further, the electrophysiological changes of ZnO NPs induced autophagy were detected by whole-cell patch-clamp. Finally, the recovery experiment was carried out by TLR4 inhibitor (TAK -242). Results: We found that ZnO NPs enhanced epilepsy susceptibility and severity. Through RNA-seq analysis and Western blot, it was found that ZnO NPs affected the changes of TLR4 and autophagy related pathways. In addition, we found that ZnO NPs mainly affects autophagy of inhibitory neurons, resulting in excitation/inhibition imbalance. The autophagy and epileptic phenotypes were reversed with TAK -242. In general, ZnO NPs exacerbate epileptic seizures by modulating the TLR4-autophagy axis. Conclusion: ZnO NPs enhanced the susceptibility and severity of epilepsy. Mechanistically, ZnO NPs affected autophagy by changing the expression of TLR4. In particular, the ZnO NPs mainly affected the synaptic function of inhibitory neuron, leading to excitation/inhibition imbalances."

基金机构："National Natural Science Foundation of China [82001378]; Young and Middle-aged Medical Excellence Team Program of Chongqing, Chongqing Chief Expert Studio program, Science and Technology Research Program of Chongqing Education Commission [KJQN202200435]; Chongqing Talents: Exceptional Young Talents Project [CQYC202005014]; China Postdoctoral Science Foundation [2023M730443]; Natural Science Foundation of Chongqing [CSTB2023NSCQ-MSX0720, CSTB2023NSCQ-JQX0035, CSTB2022NSCQ-LZX0038, cstc2021ycjh-bgzxm0035]; Joint Project of Chongqing Health Commission and Science and Technology Bureau [2023QNXM009]"

基金资助正文："Funding This study is supported by National Natural Science Foundation of China (82001378) , Young and Middle-aged Medical Excellence Team Program of Chongqing, Chongqing Chief Expert Studio program, Science and Technology Research Program of Chongqing Education Commission (KJQN202200435) , Chongqing Talents: Exceptional Young Talents Project (CQYC202005014) , China Postdoctoral Science Foundation (2023M730443) , Natural Science Foundation of Chongqing (CSTB2023NSCQ-JQX0035, CSTB2022NSCQ-LZX0038, cstc2021ycjh-bgzxm0035) , the Joint Project of Chongqing Health Commission and Science and Technology Bureau (2023QNXM009) , the Natural Science Foundation of Chongqing (CSTB2023NSCQ-MSX0720) ."