Low-Dose Exposure of Silica Nanoparticles Induces Neurotoxicity via Neuroactive Ligand–Receptor Interaction Signaling Pathway in Zebrafish Embryos

OBJECTIVE: Silica nanoparticles (SiO(2) NPs) have been extensively employed in biomedical field. SiO(2) NPs are primarily designed to enter the circulatory system; however, little information is available on potential adverse effects of SiO(2) NPs on the nervous system. METHODS: The neurotoxicity of SiO(2) NPs at different concentrations (3, 6, 12 ng/nL) on zebrafish embryos was determined using immunofluorescence and microarray techniques, and subsequently confirmed by qRT-PCR. RESULTS: SiO(2) NPs disrupt the axonal integrity and decrease the length of axons in Tg (NBT: EGFP) transgenic lines. The number of apoptotic cells in the brain and central nervous system of zebrafish embryos was increased in the presence of 12 ng/nL of SiO(2) NPs, but the difference did not reach statistical significance. Screening for changes in the expression of genes involved in the neuroactive ligand–receptor interaction pathway was performed by microarray and confirmed by qRT-PCR. These analyses demonstrated that SiO(2) NPs markedly downregulated genes associated with neural function (grm6a, drd1b, chrnb3b, adrb2a, grin2ab, npffr2.1, npy8br, gabrd, chrma3, gabrg3, gria3a, grm1a, adra2b, and glra3). CONCLUSION: The obtained results documented that SiO(2) NPs can induce developmental neurotoxicity by affecting the neuroactive ligand–receptor interaction signaling pathway. This new evidence may help to clarify the mechanism of SiO(2) NPs-mediated neurotoxicity.