Neurodevelopmental toxicity of silver nanoparticles (AgNPs) remains
largely unknown. In this study, we applied a neurosphere assay for
neurodevelopmental effects of AgNPs. The neural stem cells were isolated from rat
mesencephalon. They were cultured as a sphere. In an assay with coated plates, cells
appeared by anchoraging on the dish and then started to migrate along the radial axis
from the neurosphere. AgNPs inhibited cell migration in a dose-dependent manner.
There was a linear correlation between the inhibition of migration and the logarithm of the particle
concentration (1.25–10 μg/ml); the half-maximal inhibitory concentration was 0.41 μg/ml for 16-h
exposure. Preceding migrated cells were retarded and/or collapsed by exposure to AgNPs: lower
doses of AgNPs (0.31–1.2 μg/ml) caused a 42% retardation for 48 h, while higher doses of AgNPs
(2.5–10 μg/ml) collasped migrating cells. Furthermore, collapsed cells were TUNEL-positive and
showed a defect in the mitochondrial membrane potential. Thus, we showed the neurodevelopmental
toxicity of AgNPs using an in vitro neurosphere assay system.
Keywords: Apoptosis, migration, neural stem cell, neurosphere, repulsion, silver nanoparticle.
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