The cellular and genomic response of rat dopaminergic neurons (N27) to coated nanosilver

• Published in: Neurotoxicology (Park Forest South) Vol. 45; pp. 12 - 21
• Main Authors: Chorley, Brian, Ward, William, Simmons, Steven O., Vallanat, Beena, Veronesi, Bellina
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2014; Elsevier
• Subjects: Animals; Biological and medical sciences; Capping; Cell Line; Coated Materials, Biocompatible - toxicity; Cross-disciplinary physics: materials science; rheology; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Exact sciences and technology; Gene Expression; Materials science; Medical sciences; Metal Nanoparticles - chemistry; Metal Nanoparticles - toxicity; Mice; Microglia - drug effects; Microglia - pathology; Nanoscale materials and structures: fabrication and characterization; Nanosilver; Nanotoxicity; Oxidative Stress; Particle Size; Physics; Polyvinylpyrrolidone; Rats; Silver - toxicity; Surface coating; Toxicology; Nanotoxicity; Capping; Nanosilver; Polyvinylpyrrolidone; Surface coating; Rat; Nanoparticle; Toxicity; Genomics; Rodentia; Polymer; Genetic determinism; In vitro; Povidone; Response; Plasma substitute; Vertebrata; Mammalia; Pyrrolidone(vinyl) polymer; Animal; Genetics; Dopaminergic neuron; Nanostructured materials
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2014.08.010

This graphic depicts the questions asked in this study. Are nanoAg particles of different sizes and coatings, neurotoxic to cultured dopaminergic neurons (N27)? Is this toxicity influenced by the particles’ size or coating? •The current study examines if coated (PVP, citrate) nanoAg is differentially neurotoxic to dopaminergic neurons (N27).•Cellular and genomic data indicate that both sizes of PVP-coated material are more bioactive than citrate-coated nanoAg.•PVP-coated 75nm alters genomic pathways associated with mitochondrial dysfunction and PVP-10nm nanoAg preferentially alters ARE/NRF2 oxidative stress protective pathways. This study examined if nanosilver (nanoAg) of different sizes and coatings were differentially toxic to oxidative stress-sensitive neurons. N27 rat dopaminergic neurons were exposed (0.5–5ppm) to a set of nanoAg of different sizes (10nm, 75nm) and coatings (PVP, citrate) and their physicochemical, cellular and genomic response measured. Both coatings retained their manufactured sizes in culture media, however, the zeta potentials of both sizes of PVP-coated nanoAg were significantly less electronegative than those of their citrate-coated counterparts. Markers of oxidative stress, measured at 0.5–5ppm exposure concentrations, indicated that caspase 3/7 activity and glutathione levels were significantly increased by both sizes of PVP-coated nanoAg and by the 75nm citrate-coated nanoAg. Both sizes of PVP-coated nanoAg also increased intra-neuronal nitrite levels and activated ARE/NRF2, a reporter gene for the oxidative stress-protection pathway. Global gene expression on N27 neurons, exposed to 0.5ppm for 8h, indicated a dominant effect by PVP-coated nanoAg over citrate. The 75nm PVP-coated material altered 196 genes that were loosely associated with mitochondrial dysfunction. In contrast, the 10nm PVP-coated nanoAg altered 82 genes that were strongly associated with NRF2 oxidative stress pathways. Less that 20% of the affected genes were shared by both sizes of PVP-coated nanoAg. These cellular and genomic findings suggest that PVP-coated nanoAg is more bioactive than citrate-coated nanoAg. Although both sizes of PVP-coated nanoAg altered the genomic expression of N27 neurons along oxidative stress pathways, exposure to the 75nm nanoAg favored pathways associated with mitochondrial dysfunction, whereas the 10nm PVP-coated nanoAg affected NRF2 neuronal protective pathways.