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

Int J Mol Sci. 2021 Nov 24;22(23):12706. doi: 10.3390/ijms222312706.

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.

Keywords: active allothetic place avoidance task; hippocampus; inflammation; nanoparticle coating; neurotransmitters; silver nanoparticles; spatial long- and short-term memory.

MeSH terms

  • Animals
  • Citrates / chemistry
  • Citrates / toxicity
  • Cognition Disorders / chemically induced
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology*
  • Cytokines / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Male
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / toxicity*
  • Rats
  • Rats, Wistar
  • Serum Albumin, Bovine / chemistry
  • Serum Albumin, Bovine / toxicity*
  • Silver / chemistry*

Substances

  • Citrates
  • Cytokines
  • Serum Albumin, Bovine
  • Silver
  • Polyethylene Glycols