Maternal exposure to silver nanoparticles are associated with behavioral abnormalities in adulthood: Role of mitochondria and innate immunity in developmental toxicity

Back ground and aim: Silver nanoparticles Ag-NPs are currently used in a wide range of consumer products. Considering the small size of Ag-NPs, they are able to pass through variety of biological barriers and exert their effects. In this regard, the unique physicochemical properties of Ag-NPs along with its high application in the industry have raised concerns about their negative effects on human health. it investigated whether prenatal exposure to low doses of Ag-NPs is able to induce any abnormality in the cognitive and behavioral performance of adult offspring.Material and methods: We gavaged pregnant NMRI mice with, 1 Deionized water as vehicle, 2 Ag-NPs 10 nm 0.26 mg/kg/day , 3 Ag-NPs 30 nm 0.26 mg/kg/day , and 4 AgNO3 0.26 mg/kg/day from gestational day GD 0 until delivery day.Results: At the postnatal day PD 1, our results showed that high concentration of silver is present in the brain of pups. Further, we observed mitochondrial dysfunction and upregulation of the genes relevant to innate immune system in the brain. At PD 60, results revealed that prenatal exposure to Ag-NPs provoked severe cognitive and behavioral abnormalities in male offspring. In addition, we found that prenatal exposure to Ag-NPs was associated with abnormal mitochondrial function and significant up-regulation of the genes relevant to innate immunity in the brain. Although the Ag-NPs have been considered as safe compounds at low doses, our results indicate that prenatal exposure to low doses of Ag-NPs is able to induce behavioral and cognitive abnormalities in adulthood. Also, we found that these effects are at least partly associated with hippocampal mitochondrial dysfunction and the activation of sterile inflammation during early stages of life.Conclusion: In conclusion, results of this study suggest that prenatal exposure to low dose of Ag-NPs can seriously affect brain and behavior in adult male mice possibly through altering the brain mitochondrial function and innate immunity. However, more studies are necessary to determine the mechanisms through which Ag-NPs negatively affect the neurodevelopment and behavior.

Keywords:

Behavioral dysfunction , Hippocampus , Innate immunity , Mitochondria , Prenatal stage , Silver nanoparticles