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 1.0 μg/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.

Cerium oxide nanoparticles inhibit differentiation of neural stem cells

“…Nanoparticles could impact on cytoskeletal dynamics and organization directly, from within the cytoplasm, or indirectly through interactions with extracellular matrix components or transmembrane receptors ( e.g ., integrins). Interestingly, a recent study has shown that sublethal concentrations of silver nanoparticles disrupted cytoskeletal organization and neurite extension in cultured adult neural stem cells derived from rat brain, likely through a direct effect on actin dynamics 64 . In contrast, our results suggested an effect of nanoceria at the transcriptional level in differentiating neural stem cells.…”

Gut Dysbiosis and Neurobehavioral Alterations in Rats Exposed to Silver Nanoparticles

“…Past studies with varying length to AgNP exposure in rodents and fish suggest that these chemicals can result in several neuropathological changes, such as edema formation, neuronal degradation and apoptosis, synaptic degeneration, tight junction disruptions, increase in reactive oxygen species (ROS), disturb brain antioxidant system, amyloid-β (Aβ) plagues, and astrocyte swelling 15-18, 20, 22, 23, 26-31, 49-52 . AgNPs may also disrupt the cytoskeleton architecture in neuronal cells 53 . Several transcripts are altered in neurons of mice or rats exposed to AgNPs, such as Psen1, Psen2, Trex1, Irf7, RasGrf1, Bcl2, Th, Maoa, Cdh1, Cldn1, and Il4 16,54,55 .…”

Nano- and neurotoxicology: An emerging discipline

“…Schematically, the presence of nanoparticles in astrocytes may participate in the induction of reactive gliosis, while in the case of nanoparticle accumulation in neurons, there may be changes in neuronal metabolism, functions, or even viability. Finally, the sub-cellular scale also has its own importance, as suggested by a study reporting the loss of β-tubulin and actin filamentin cultured neurons exposed to 20 nm silver nanoparticles (Xu et al, 2013a); this observation was reproduced at sublethal concentrations of silver nanoparticles which disrupt also actin dynamics in SVZ-NSCs (Cooper and Spitzer, 2015). Among the possible expected effects, impacts on cell morphology, function, and viability are critical for the highly vulnerable nerve cells, when compared to other cell types.…”