Abstract
Silver nanoparticles (AgNPs) are the one of the most extensively used nanomaterials. The strong antimicrobial properties of AgNPs have led to their use in a wide range of medical and consumer products. Although the neurotoxicity of AgNPs has been confirmed, the molecular mechanisms have not been extensively studied, particularly in immature organisms. Based on information gained from previous in vitro studies, in the present work, we examine whether ionotropic NMDA glutamate receptors contribute to AgNP-induced neurotoxicity in an animal model of exposure. In brains of immature rats subjected to a low dose of AgNPs, we identified ultrastructural and molecular alterations in the postsynaptic region of synapses where NMDA receptors are localized as a multiprotein complex. We revealed decreased expression of several NMDA receptor complex-related proteins, such as GluN1 and GluN2B subunits, scaffolding proteins PSD95 and SynGAP, as well as neuronal nitric oxide synthase (nNOS). Elucidating the changes in NMDA receptor-mediated molecular mechanisms induced by AgNPs, we also identified downregulation of the GluN2B-PSD95-nNOS-cGMP signaling pathway which maintains LTP/LTD processes underlying learning and memory formation during development. This observation is accompanied by decreased density of NMDA receptors, as assessed by a radioligand binding assay. The observed effects are reversible over the post-exposure time. This investigation reveals that NMDA receptors in immature rats are a target of AgNPs, thereby indicating the potential health hazard for children and infants resulting from the extensive use of products containing AgNPs.
Highlights
Rapid development of nanotechnology has occurred over the past decade
0.23 mg/kg for AgNP-treated and Ag citrate-treated rats, respectively (Figure 1C), whereas in control brain tissue, silver is below the detection limit
Since a vast majority of neurons are of glutamatergic activity and because glutamate receptors play pivotal roles in the function of the central nervous system (CNS), it would be helpful to determine whether AgNPs influence the expression and function of the NMDA
Summary
Rapid development of nanotechnology has occurred over the past decade. Silver nanoparticles (AgNPs) are among the nanomaterials which have attracted significant interest, because their unique characteristics make them useful in a wide spectrum of applications. The strong antimicrobial properties of AgNPs are of particular interest resulting in their use in medical and consumer products (for a review see [1]). Solid materials acquire various altered characteristics, the most important of which is a high surface-to-volume ratio. This feature contributes significantly to the high chemical and biological activities of nanoparticles. AgNPs are able to freely cross cellular membranes, accumulate in subcellular compartments and actively interact with biomolecules
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