Newborn neurons are damaged in vitro by a low concentration of silver nanoparticles through the inflammatory oxidative stress pathway

With increasing applications of nanomaterials, including silver nanoparticles (AgNPs), unknown potential risks are present against humans and the environment, especially to the fetus and neonates, which are more sensitive to the cytotoxicity of such agents. This study focused on the effects of AgNP exposure on newborn neurons differentiated from neural stem cells (NSCs) in vitro. We isolated NSCs from fetal rat hippocampus and incubated them in neural differentiation medium for 3-7 days to form newborn neurons and networks. After exposure to 2 μg/mL AgNPs, cell viability was reduced, and early neuronal processes and extensions were fragmented. Furthermore, AgNP treatment increased cellular superoxide dismutase activity and decreased the mitochondrial membrane potential, leading to neuronal death. AgNPs also increased the expression of FOXO3 and decreased nuclear factor-erythroid 2-related factor-2, as well as stimulated the formation of autophagosomes. Therefore, even a low concentration of AgNPs can interrupt early neuronal processes, and facilitate neuron apoptosis by increased cellular oxidative stress and mitochondrial disruption. Thus, it is necessary to note the daily exposure of nanomaterials (e.g., AgNPs) to pregnant women and infants, which may cause neurodevelopmental disorders.