Silica-coated magnetic nanoparticles activate microglia and induce neurotoxic d-serine secretion

Abstract Background Nanoparticles have been studied for brain imaging, diagnosis, and drug delivery owing to their versatile properties due small sizes. However, there are growing concerns that nanoparticles may exert toxic effects in the brain. In this study, we assessed direct nanotoxicity on microglia, resident macrophages of central nervous system, indirect toxicity neuronal cells exerted by silica-coated magnetic containing rhodamine B isothiocyanate dye [MNPs@SiO 2 (RITC)]. Methods We investigated MNPs@SiO (RITC)-induced biological changes BV2 murine microglial via RNA-sequencing-based transcriptome analysis gas chromatography-mass spectrometry-based intracellular extracellular amino acid profiling. Morphological were analyzed transmission electron microscopy. Indirect (RITC) Transwell-based coculture with (RITC)-treated microglia. mouse vivo examined immunohistochemical analysis. Results morphologically activated expression Iba1, an activation marker protein, was increased after treatment. Transmission microscopy revealed lysosomal accumulation formation vesicle-like structures cells. The several genes related metabolism inflammation altered 100 µg/ml microglia when compared non-treated (control) 10 Combined profiling analyses transport serine family acids, including glycine, cysteine, serine, enhanced. only growth medium microglia; especially, excitotoxic D -serine secretion from primary rat most strongly Activated reduced ATP levels proteasome activity cocultured cells, especially cortical neurons, secretion. Moreover, ubiquitinated proteins accumulated inclusion bodies dopaminergic neurons , (RITC), -serine, ubiquitin aggresomes distributed Conclusions triggers excitotoxicity secretion, highlighting importance neurotoxicity mechanisms incurred nanoparticle-induced activation.