Silver Impairs Neurodevelopment: Studies in PC12 Cells

Abstract

BackgroundExposure to silver is increasing because of silver nanoparticles in consumer products.Objectives and methodsMany biological effects of silver entail actions of Ag+ (monovalent silver ions), so we used neuronotypic PC12 cells to evaluate the potential for silver to act as a developmental neurotoxicant, using chlorpyrifos (CPF), a pesticide known to evoke developmental neurotoxicity, as a positive control for comparison.ResultsIn undifferentiated cells, a 1-hr exposure to 10 μM Ag+ inhibited DNA synthesis more potently than did 50 μM CPF; it also impaired protein synthesis but to a lesser extent than its effect on DNA synthesis, indicating a preferential effect on cell replication. Longer exposures led to oxidative stress, loss of viability, and reduced numbers of cells. With the onset of cell differentiation, exposure to 10 μM Ag+ evoked even greater inhibition of DNA synthesis and more oxidative stress, selectively impaired neurite formation without suppressing overall cell growth, and preferentially suppressed development into the acetylcholine phenotype in favor of the dopamine phenotype. Lowering the exposure to 1 μM Ag+ reduced the net effect on undifferentiated cells. However, in differentiating cells, the lower concentration produced an entirely different pattern, enhancing cell numbers by suppressing ongoing cell death and impairing differentiation in parallel for both neurotransmitter phenotypes.ConclusionsOur results show that silver has the potential to evoke developmental neurotoxicity even more potently than known neurotoxicants, such as CPF, and that the spectrum of effects is likely to be substantially different at lower exposures that do not show signs of outright toxicity.

Histological and immunohistochemical study on the potential toxicity of sliver nanoparticles on the structure of the spleen in adult male albino rats

“…These broad applications, however, increase human exposure and thus the potential risk related to their short-and long-term toxicity [7] . The health effects of this material have not been well characterized even though the toxicity of nanosilver has been demonstrated in vitro models [8] .…”

SNF1/AMP-Activated Protein Kinases: Genes, Expression and Biological Role

“…There is data that silver nanoparticles are more toxic than silver microparticles or ions [51][52][53]. Powers et al [53] have shown that silver nanoparticles have the potential to evoke developmental neurotoxicity even more potently than known neurotoxicants.…”

“…Powers et al [53] have shown that silver nanoparticles have the potential to evoke developmental neurotoxicity even more potently than known neurotoxicants. Silver ions inhibited replication and increased cell death in undifferentiated cells, and selectively impaired neurite formation.…”

Impacts of Silver Nanoparticle Ingestion on Pigmentation and Developmental Progression in Drosophila

“…The toxicity of silver nanoparticles (Ag NP) has been documented in a large number of in vitro studies using a number of cell lines including but not limited to human hepatoma cells , PC12 neuronal cells (Powers et al, 2010), BRL3A rat liver cells, germline stem cells (Braydich-Stolle et al, 2005), human lung fibroblasts, and gliablastoma cells (AshaRani et al, 2009). However, a fewer number of in vivo studies using animal models has been conducted Ahamed et al, 2010b;Posgai et al, 2009;Kumari et al, 2009;Li et al, 2010;Wu et al, 2009).…”