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

Abstract

Jialiu Wei,1 Jianhui Liu,2 Shuang Liang,2 Mengqi Sun,2 Junchao Duan2 1Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Junchao DuanDepartment of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, People’s Republic of ChinaEmail [email protected]: Silica nanoparticles (SiO2 NPs) have been extensively employed in biomedical field. SiO2 NPs are primarily designed to enter the circulatory system; however, little information is available on potential adverse effects of SiO2 NPs on the nervous system.Methods: The neurotoxicity of SiO2 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: SiO2 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 SiO2 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 SiO2 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 SiO2 NPs can induce developmental neurotoxicity by affecting the neuroactive ligand–receptor interaction signaling pathway. This new evidence may help to clarify the mechanism of SiO2 NPs-mediated neurotoxicity.Keywords: silica nanoparticles, neurotoxicity, neuroactive ligand–receptor interaction signaling pathway, zebrafish

Keywords

• silica nanoparticles
• neurotoxicity
• neuroactive ligand-receptor interaction signaling pathway
• zebrafish