Silver nanoparticles (AgNPs) cause degeneration of cytoskeleton and disrupt synaptic machinery of cultured cortical neurons

Abstract

BackgroundSilver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.ResultsHere we examine the effects of ultra fine scales (20 nm) of AgNPs at various concentrations (1, 5, 10 and 50 μg/ml) on primary rat cortical cell cultures. We found that AgNPs (at 1-50 μg/ml) not only inhibited neurite outgrowth and reduced cell viability of premature neurons and glial cells, but also induced degeneration of neuronal processes of mature neurons. Our immunocytochemistry and confocal microscopy studies further demonstrated that AgNPs induced the loss of cytoskeleton components such as the β-tubulin and filamentous actin (F-actin). AgNPs also dramatically reduced the number of synaptic clusters of the presynaptic vesicle protein synaptophysin, and the postsynaptic receptor density protein PSD-95. Finally, AgNP exposure also resulted in mitochondria dysfunction in rat cortical cells.ConclusionsTaken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.

Toxic effects of silver nanoparticles in mammals – does a risk of neurotoxicity exist?

“…Many of the results show that exposure to AgNPs causes decreased cell viability, mainly of neurons [20,52,54,59,137,144,146,148]. In the case of astroglia-rich primary cultures, the results are generally inconsistent with either no changes in viability observed after incubation with AgNPs [85] or observations of high sensitivity [52].…”

“…Such differences are likely related to both the incubation time and the size of the AgNPs. Moreover, it was observed that AgNPs may negatively influence proliferation of human cerebral cells [20] and axonal outgrowth of premature neurons and glial cells [144].…”

Cytotoxicity and antibiofilm activity of SiO2/cellulose derivative hybrid materials containing silver nanoparticles

“…These data suggested that cell adhesion on SiO 2 /HPC/Ag and SiO 2 /HPMC/Ag materials was affected by addition of silver into hybrids as other authors reported the alteration in cell morphology and cytoskeleton structures in contact with Ag content (Asharani et al, 2009;Xu et al, 2013). That is most probably due to alteration of the cytoskeletal actin pathway (Xu et al, 2013) due to the downregulation of major actin-binding proteins like filamin, as Asharani et al (2009) reported. On the other hand, the above results suggest that cell adhesion is strongly affected and depends on the surface roughness of obtained hybrid materials.…”

Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles

“…14,15 The employed endocytic mechanism determines the rate of uptake, intracellular fate, NP retention, and also influences the negative effects of NP presence. Internalized NPs can sterically hinder the cellular processes and cause cell stress, which manifests as lower proliferation rate, 16 induction of oxidative stress, 17,18 cytoskeleton disruption, 19 hindered differentiation, [20][21][22][23] and DNA damage. 24 NPs can also cause autophagy and lysosomal dysfunctions 25 and other effects, which can eventually trigger apoptosis 21,26 or induce necrosis.…”