Silver Nanoparticles Suppress Retinoic Acid-Induced Neuronal Differentiation in Human-Derived Neuroblastoma SH-SY5Y Cells

Abstract

Nanoparticles are being used in an increasing number of applications in a wide range of fields; however, these particles can migrate to the brain, raising concerns over their potential as risk factors of neurodevelopment disorders. Here, we examined the effects of silver nanoparticles with a diameter of 10 nm (nAg10) on neural differentiation in human-derived neuroblastoma SH-SY5Y cells. SH-SY5Y cells treated with retinoic acid undergo neuronal differentiation characterized by increased expression of brain-derived neurotrophic factor (BDNF); however, co-treatment of these cells with retinoic acid (RA) and nAg10 significantly mitigated this RA-induced BDNF expression. RA-induced neurite outgrowth and extracellular secretion of dopamine were significantly suppressed by nAg10 in a concentration-dependent manner. Reactive oxygen species (ROS) production was enhanced in cells co-treated with RA and nAg10, and the expression level of BDNF was restored by co-treatment with nAg10 and an ROS inhibitor (N-acetylcysteine). nAg10-induced mitochondrial ROS production and decreased mitochondrial fusion-related gene expression. In summary, nAg10 suppressed retinoic acid-induced neuronal differentiation in SH-SY5Y cells via the oxidative stress pathway, induced mitochondrial ROS production, and decreased mitochondrial fusion-related gene expression.

Cellular Lipidome Changes during Retinoic Acid (RA)-Induced Differentiation in SH-SY5Y Cells: A Comprehensive In Vitro Model for Assessing Neurotoxicity of Contaminants

“…A limitation of in vivo models, which primarily use rats, mice, zebrafish, and other nonmammalian organisms, is that they might not recapitulate mechanisms specific to humans due to differences in gene expression or regulatory mechanisms that differ in these organisms. , For this reason, various in vitro models using human cell lines have been pursued commonly. The human neuroblastoma cell line SH-SY5Y has been widely used as an in vitro model to study potential neurotoxic effects of environmental contaminants and xenobiotics , and various neurological conditions such as neurotrauma, neurotoxicity, neurodegeneration and relevant neurodegenerative diseases. , …”

“…3,4 For this reason, various in vitro models using human cell lines have been pursued commonly. The human neuroblastoma cell line SH-SY5Y has been widely used as an in vitro model 5 to study potential neurotoxic effects of environmental contaminants and xenobiotics 6,7 and various neurological conditions such as neurotrauma, 8 neurotoxicity, 9 neurodegeneration 10 and relevant neurodegenerative diseases. 11,12 Strong evidence exists that the developing brain is most vulnerable to toxic chemical exposure when neuronal differentiation occurs in the central nervous system, during which mature neurons form along with an interconnected network of cells capable of processing a conglomerate of information.…”