Size-dependent impairment of cognition in mice caused by the injection of goldnanoparticles

Abstract

We explored the size-dependent impairment of cognition in mice caused by theinjection of gold nanoparticles (GNPs). GNPs of 17 and 37 nm in diameter wereinjected intraperitoneally into BALB/c mice at doses ranging from 0.5 to14.6 mg kg − 1. ICP-MS was performed on brain tissue collected 1, 14 and 21 days after the injection. Apassive-avoidance test was performed on day 21. Monoamine levels were determined on day21. The microscopic distribution of GNPs in the hippocampus was examined usingcoherent anti-Stokes Raman scattering (CARS) microscopy and transmission electronmicroscopy (TEM).The results indicated that 17 nm GNPs passed through the blood–brain barrier morerapidly than 37 nm GNPs. Treatment with 17 nm GNPs decreased the latency time, whichwas comparable to the effect of scopolamine treatment, while 37 nm GNPs showed nosignificant effect. Dopamine levels and serotonin levels in the brain were significantlyaltered by the injection of 17 and 37 nm GNPs. GNPs affected dopaminergic andserotonergic neurons. CARS microscopy indicated that 17 nm GNPs entered the CornuAmmonis (CA) region of the hippocampus, while 37 nm GNPs were excluded from the CAregion. TEM verified the presence of 17 nm GNPs in the cytoplasm of pyramidal cells.In this study, we showed that the ability of GNPs to damage cognition in micewas size-dependent and associated with the ability of the particles to invade thehippocampus. The dosage and duration of the treatment should be taken into account ifGNPs are used in the future as vehicles to carry therapeutic agents into the brain.