Silver nanoparticles at sublethal concentrations disrupt cytoskeleton and neurite dynamics in cultured adult neural stem cells

Abstract

Silver nanoparticles (AgNPs) have potent antimicrobial properties at concentrations far below those that cause cytotoxic and genotoxic effects in eukaryotic cells. This property has resulted in the widespread use of AgNPs in consumer products, leading to environmental exposures at sub-lethal levels through ingestion and inhalation. Although the toxicity of AgNPs has been well characterized, effects of environmentally relevant exposures have not been extensively investigated in spite of studies that suggest accumulation of silver in tissues, including brain. To assess the sublethal effects of AgNPs on neural cell function, we used cultured SVZ-NSCs, a model of neurogenesis and neural cells. Throughout life, neural stem cells (NSCs) in the subventricular zone (SVZ) of the lateral ventricles proliferate and migrate via the rostral migratory stream to the olfactory bulb. Once there, they complete differentiation into neurons and glia and integrate into existing circuits. This process of neurogenesis is tightly regulated, and is considered a part of healthy brain function. We found that 1.0μg/mL AgNP exposure in cultured differentiating NSCs induced the formation of f-actin inclusions, indicating a disruption of actin function. These inclusions did not co-localize with AgNPs, and therefore do not represent sequestered nanoparticles. Further, AgNP exposure led to a reduction in neurite extension and branching in live cells, cytoskeleton-mediated processes vital to neurogenesis. We conclude that AgNPs at sublethal concentrations disrupt actin dynamics in SVZ-NSCs, and that an associated disruption in neurogenesis may contribute to documented deficits in brain function following AgNP exposure.