Four types of inorganic nanoparticles stimulate the inflammatory reaction in brain microglia and damage neurons in vitro

Once nanoparticles enter the central nervous system (CNS), they immediately encounter a complex environment of resident microglial immune cell and neurons. In the present study, NPs of 20-60 nm in diameter (SiO2-NPs, TiO2-NPs, HAP-NPs and Fe3O4-NPs) were evaluated for their ability to induce microglia-mediated neurodegeneration. The microglia were directly exposed to NPs. The results showed that both TiO2-NPs and HAP-NPs induced significant iNOS expression, resulting in NO release from the microglia. The expression levels of MCP-1 and MIP-1 alpha were also upregulated. These activation effects were accompanied by the activation of the transcription factor NF-kappa B. In addition, the secretion levels of TNF-alpha, IL-1 beta and IL-6 were variably increased by all four NPs. Subsequently, the cell-free supernatants from microglia monocultures were harvested and tested for their ability to stimulate PC12 cells. The results demonstrated that microglia-derived soluble factors induced by TiO2-NPs suppressed Th gene expression, and those by TiO2-NPs and HAP-NPs caused cytotoxicity in PC12 cells. Taken together, these results suggest that the NPs induced microglial activation and subsequently caused the release of proinflammatory factors that contributed to the dysfunction and cytotoxicity in PC12 cells. (c) 2012 Elsevier Ireland Ltd. All rights reserved.