Silver nanoparticles have been widely used in the lighting and food industries, in medicine, and in pharmaceutics as an antiseptic agent. Recent research demonstrates that, after prolonged oral administration, silver nanoparticles may cross the blood-brain barrier and accumulate in the brain in rather high amounts. In ex vivo experiments, it has also been shown that silver nanoparticles demonstrate neurotoxicity. The objective of this work was to answer the questions whether silver nanoparticles change cognitive and behavioral functions of mammals after prolonged administration if silver nanoparticles have accumulated in the brain. C57Bl/6 male mice were orally exposed to PVP-coated silver nanoparticles daily for 30, 60, 120 and 180 days. Control mice were exposed to distilled water. After that they were tested in the Open Field, Elevated Plus Maze, Light-Dark Box and contextual fear conditioning task. The data have shown that the experimental mice went through three periods of switching in the behavior caused by adaptation to the toxic silver nanoparticles: anxiety, appearance of research instinct and impairment of long-term memory. This provides evidence of the hazardous effect of silver nanoparticles, which appears after long periods of silver nanoparticle oral administration.

The influence of daily prolonged administration of silver nanoparticles on the cognitive functions of a model mammal was studied. The accumulation of silver in the whole brain and the hippocampus, cerebellum, cortex and residual brain tissue of the mouse was investigated by highly precise and representative neutron activation analysis, and histological studies were conducted. Here, we show that long-term memory impairments were caused by the accumulation of silver nanoparticles in the brain and its subregions, such as the hippocampus, cerebellum and cortex, in a step-like manner by disturbance of hippocampal cell integrity. Three different approaches allowed us to observe this phenomenon and discover the reasons it occurred.

We studied the effect of human lactoferrin (hLf) on degenerative changes in the nigrostriatal system and associated behavioral deficits in the animal model of Parkinson disease. Nigrostriatal dopaminergic injury was induced by single administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 40 mg/kg) to five-month-old C57Bl/6 mice. Behavioral disturbances were assessed in the open field and rotarod tests and by the stride length analysis. Structural deficits were assessed by the counts of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra and optical density (OD) of TH-immunolabeled fibers in the striatum. Acute MPTP treatment induced long-term behavioral deficit and degenerative changes in the nigrostriatal system. Pretreatment with hLf prevented body weight loss and promoted recovery of motor functions and exploratory behavior. Importantly, OD of TH-positive fibers in the striatum of mice treated with hLf almost returned to normal, and the number of TH-positive cells in the substantia nigra significantly increased on day 28. These results indicate that hLf produces a neuroprotective effect and probably stimulates neuroregeneration under conditions of MPTP toxicity in our model. A relationship between behavioral deficits and nigrostriatal system disturbances at delayed terms after MPTP administration was found.

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Since ancient times, silver has been known for its pronounced bactericidal, antiviral and fungicidal properties. Currently, nanoparticles of this metal are widely used in the food, light and pharmaceutical industries, as well as in medicine. Silver in any form can have a toxic effect not only on pathogens, but also on healthy cells. The biological activity and bioavailability of silver preparations depend on the degree of their solubility in water. In addition, the maximum permissible concentration of soluble forms of silver is an order of magnitude lower than that of insoluble forms. This makes nanoparticles of silver with a hydrophilic coating that form stable colloidal solutions in aqueous media potentially unsafe objects. In this work, we studied the kinetics of the accumulation of silver nanoparticles with an average size of 34 ± 5 nm stabilized with polyvinylpyrrolidone in the organs of laboratory C57Bl/6 mice. The administration of nanoparticles was carried out orally for 30, 60, 120 and 180 days at the dose of 50 µg/day/animal. All the mice developed and gained weight normally during the experiment. No adverse effects were observed. Determination of the silver content in biological tissues of mammals was accomplished by neutron activation analysis. The masses and concentrations of silver in the brain and its different sections (hippocampus, cerebellum, cortex and remnants), as well as in the lungs, testes, liver, blood, kidneys, spleen and heart, were determined. The injection times at which the accumulation curves reached saturation were established. An extremely high accumulation of silver in the testes was shown at 120 days of administration, and a significant accumulation of silver in the lungs and brain was observed. The accumulation of silver in all parts of the brain except the cortex was significant, and its trend was similar to that in the whole brain.