1. Academic Validation
  2. NOX2 activation contributes to cobalt nanoparticles-induced inflammatory responses and Tau phosphorylation in mice and microglia

NOX2 activation contributes to cobalt nanoparticles-induced inflammatory responses and Tau phosphorylation in mice and microglia

  • Ecotoxicol Environ Saf. 2021 Dec 1;225:112725. doi: 10.1016/j.ecoenv.2021.112725.
Jing Li 1 Junxiang Wang 1 Yuan-Liang Wang 1 Zhousong Luo 1 Chunyan Zheng 1 Guangxia Yu 1 Siying Wu 2 Fuli Zheng 3 Huangyuan Li 4
Affiliations

Affiliations

  • 1 Fujian Key Lab of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, China; Department of Preventive Medicine, School of Public Health, Fujian Medical University, China.
  • 2 Fujian Key Lab of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, China; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, China; Key Lab of Environment and Health, School of Public Health, Fujian Medical University, China. Electronic address: sywu@fjmu.edu.cn.
  • 3 Fujian Key Lab of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, China; Department of Preventive Medicine, School of Public Health, Fujian Medical University, China. Electronic address: F.zheng@fjmu.edu.cn.
  • 4 Fujian Key Lab of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, China; Department of Preventive Medicine, School of Public Health, Fujian Medical University, China; Key Lab of Environment and Health, School of Public Health, Fujian Medical University, China. Electronic address: lhy@fjmu.edu.cn.
Abstract

Despite the wide application of cobalt nanoparticles (CoNPs), its neurotoxicity and the underlying mechanisms are not fully understood. In this study, CoNPs-induced toxic effect was examined in both C57BL/6J mice and microglial BV2 cells. CoNPs-induced brain weight loss and the reduction of Nissl bodies, assuring neural damage. Moreover, both total unphosphorylated Tau and phosphorylated Tau (pTau; T231 and S262) expressions in the hippocampus and cortex were upregulated, unveiling Tau phosphorylation. Besides, the increase in inflammation-related proteins NLRP3 and IL-1β were found in mice brain. Corroborating that, microglial marker Iba-1 expression was also increased, suggesting microglia-involved inflammation. Among the NADPH Oxidase (NOX) family proteins tested, only NOX2 was activated by CoNPs in hippocampus. Therefore, BV2 cells were employed to further investigate the role of NOX2. In BV2 cells, NOX2 expression was upregulated, corresponding to the production of ROS. Moreover, similar induction in Tau phosphorylation and inflammation-related protein expressions were observed in CoNPs-exposed BV2 cells. Treatment of apocynin, a NOX2 Inhibitor, reduced ROS generation and reversed Tau phosphorylation and inflammation caused by CoNPs. Thus, CoNPs induced ROS production, Tau phosphorylation and inflammation specially via NOX2 activation.

Keywords

CoNPs; Inflammation; Microglia; NOX2; Tau phosphorylation.

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