Silver Nanoparticles Impair Cognitive Functions and Modify the Hippocampal Level of Neurotransmitters in a Coating-Dependent Manner

Abstract

Due to their potent antibacterial properties, silver nanoparticles (AgNPs) are widely used in industry and medicine. However, they can cross the brain–blood barrier, posing a risk to the brain and its functions. In our previous study, we demonstrated that oral administration of bovine serum albumin (BSA)-coated AgNPs caused an impairment in spatial memory in a dose-independent manner. In this study, we evaluated the effects of AgNPs coating material on cognition, spatial memory functioning, and neurotransmitter levels in rat hippocampus. AgNPs coated with BSA (AgNPs(BSA)), polyethylene glycol (AgNPs(PEG)), or citrate (AgNPs(Cit)) or silver ions (Ag+) were orally administered at a dose of 0.5 mg/kg b.w. to male Wistar rats for a period of 28 days, while the control (Ctrl) rats received 0.2 mL of water. The acquisition and maintenance of spatial memory related to place avoidance were assessed using the active allothetic place avoidance task, in which rats from AgNPs(BSA), AgNPs(PEG), and Ag+ groups performed worse than the Ctrl rats. In the retrieval test assessing long-term memory, only rats from AgNPs(Cit) and Ctrl groups showed memory maintenance. The analysis of neurotransmitter levels indicated that the ratio between serotonin and dopamine concentration was disturbed in the AgNPs(BSA) rats. Furthermore, treatment with AgNPs or Ag+ resulted in the induction of peripheral inflammation, which was reflected by the alterations in the levels of serum inflammatory mediators. In conclusion, depending on the coating material used for their stabilization, AgNPs induced changes in memory functioning and concentration of neurotransmitters.

Coating-Dependent Neurotoxicity of Silver Nanoparticles—An In Vivo Study on Hippocampal Oxidative Stress and Neurosteroids

“…Results obtained by Recordati et al showed high deposition of silver in the brain after oral exposure of environmentally relevant dose of citrate-coated AgNPs at the end of the administration as well as after 4 weeks of recovery that highlighted slow elimination of Ag from the brain structures [23]. Our previous study has also shown that oral administration of AgNPs at a relatively small concentration resulted in a time-dependent accumulation of silver in the brain, particularly in the hippocampus, and simultaneous deterioration of learning skills in rats [16,24]. Additionally, our recent studies demonstrated that the effect of AgNPs on cognitive functions is determined by the coating used for the stabilization of these nanoparticles.…”

“…The behavioral test used to assess learning skills in these rats revealed impaired formation and consolidation of memory traces in the AgNPs(BSA)-treated group. The effects of this impairment were shown to be deficits of memory acquisition and maintenance of long-term memory [24]. Other authors also observed steroid-related behavioral disorders, including anxiety-like behavior in mice exposed to citrate-coated AgNPs [45].…”

“…Additionally, our recent studies demonstrated that the effect of AgNPs on cognitive functions is determined by the coating used for the stabilization of these nanoparticles. It was found that exposure to AgNPs coated with BSA and PEG, as well as AgNO 3 as a source of Ag + , was associated with impairment of hippocampal-dependent cognitive functions [24]. Taking into account the results of our studies and the possible toxicity of AgNPs toward the central nervous system (CNS), in the present study we investigated the mechanisms underlying the observed impairment of cognition functions after oral administration of AgNPs at environmentally relevant concentrations.…”

Biomimetic nanoparticles for tumor immunotherapy

“…Platelets (PLT) are circulatory guards in the blood stream and have chemotactic effects on damaged vasculature and tumor tissue. Recent studies have shown that PLT membranes can be used as biomimetic coatings Figure 4 , ( Jiang et al, 2020 ; Dziendzikowska et al, 2021 ). Plasma membranes derived from human platelets have a variety of proteins, glycoproteins, and lipids and possess platelet-like properties, such as the ability to avoid macrophage recognition, capture of circulating tumor cells, and homing to inflammatory sites ( Dziendzikowska et al, 2021 ).…”

“…Recent studies have shown that PLT membranes can be used as biomimetic coatings Figure 4 , ( Jiang et al, 2020 ; Dziendzikowska et al, 2021 ). Plasma membranes derived from human platelets have a variety of proteins, glycoproteins, and lipids and possess platelet-like properties, such as the ability to avoid macrophage recognition, capture of circulating tumor cells, and homing to inflammatory sites ( Dziendzikowska et al, 2021 ). Bahmani et al reported the development of a PLTs-membrane coated nanoparticle (PNP) specifically designed for intratumoral delivery of resiquimod (R848) to treat solid tumors ( Bahmani et al, 2021 ).…”