Abstract
Due to strong antimicrobial properties, silver nanoparticles (AgNPs) are used in a wide range of medical and consumer products, including those dedicated for infants and children. While AgNPs are known to exert neurotoxic effects, current knowledge concerning their impact on the developing brain is scarce. During investigations of mechanisms of neurotoxicity in immature rats, we studied the influence of AgNPs on glutamate transporter systems which are involved in regulation of extracellular concentration of glutamate, an excitotoxic amino acid, and compared it with positive control—Ag citrate. We identified significant deposition of AgNPs in brain tissue of exposed rats over the post-exposure time. Ultrastructural alterations in endoplasmic reticulum (ER) and Golgi complexes were observed in neurons of AgNP-exposed rats, which are characteristics of ER stress. These changes presumably underlie substantial long-lasting downregulation of neuronal glutamate transporter EAAC1, which was noted in AgNP-exposed rats. Conversely, the expression of astroglial glutamate transporters GLT-1 and GLAST was not affected by exposure to AgNPs, but the activity of the transporters was diminished. These results indicate that even low doses of AgNPs administered during an early stage of life create a substantial risk for health of immature organisms. Hence, the safety of AgNP-containing products for infants and children should be carefully considered.
Highlights
Silver nanoparticles (AgNPs) have strong antimicrobial potential and are included in a wide range of medical and consumer products, some of which are used by infants and children such as food handling devices, baby bottles, pacifiers, toys, blankets, clothes, or cleaning products [1,2]
We focused on examining the expression and function of three main glutamate transporters: neuronal excitatory amino acid carrier 1 (EAAC1) and two glial transporters, glutamate/aspartate transporter (GLAST) and glutamate transporter 1 (GLT-1)
The early and late effects of prolonged exposure to AgNPs were assessed at Postnatal Days (PND) 35 and 90, respectively, and compared with effects produced by treatment with ionic silver
Summary
Silver nanoparticles (AgNPs) have strong antimicrobial potential and are included in a wide range of medical and consumer products, some of which are used by infants and children such as food handling devices, baby bottles, pacifiers, toys, blankets, clothes, or cleaning products [1,2]. In vivo evidence for a toxic influence of AgNPs on glial cells has been scarce Likewise, it is not known whether the deleterious changes observed in neurons of exposed animals are directly caused by AgNPs or are an indirect result of disturbed neuroprotective function of astroglial cells. Considering the fact that the developing brain is highly susceptible to different toxins [15] and that research on the influence of AgNPs on immature brain has been scarce, there is an urgent need to investigate the mechanisms of neurotoxicity induced by AgNPs. in the current study, we applied a model of developmental exposure to a low dose of AgNPs. Since previously published data provide indications that AgNPs induce neuronal injury, the current studies were undertaken to search for a contribution of glutamate transporters to this mechanism. The early and late effects of prolonged exposure to AgNPs were assessed at Postnatal Days (PND) 35 and 90, respectively, and compared with effects produced by treatment with ionic silver
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