Effects of prenatal exposure to silver nanoparticles on spatial cognition and hippocampal neurodevelopment in rats

Silver nanoparticles (Ag-NPs) are among the most commonly used nanomaterials and may be exposed to human and ecosystem. Prior in vitro study showed that Ag-NPs compromised neurodevelopment of PC12 cells. This study aims to investigate the effect of prenatal exposure to Ag-NPs on spatial cognition and hippocampal neurodevelopment in rats.Pregnant rats were exposed by intraperitoneal injection to various solutions during pregnancy, including vehicle (water and glycerol mixture, 1:1 in volume), uncoated Ag-NPs (0.427mg Ag perg rat), polyvinylpyrrolidine (PVP)-coated Ag-NPs (0.407mg Ag perg rat), silver nitrate (0.013mg Ag+ and 0.007mg NO3+ per g rat) and sodium nitrate (0.007mg NO3+ perg rat). Pregnant rats without any injection were used as blank control. Male offspring at postnatal day 35 (PND35) were randomly selected for Morris Water Maze (MWM) test. After the MWM test, the rats were decapitated and hippocampus were collected for analysis of tissue structure, silver content, GAP-43 mRNA and protein expressions.For the spatial learning in MWM test, since the third test day, the escape latency of rats in the uncoated Ag-NPs group was significantly higher than those in the other groups. The behaviors of rats were not significantly different among the other groups. The averaged silver content in the hippocampus of rats in the uncoated Ag-NPs group was 17.51μg/g, significantly higher than those in the other groups. The hippocampal structure in rats of the uncoated Ag-NPs group was deformed as compared to those in the other groups. Compared with the rats in blank and vehicle controls, the levels of GAP-43 mRNA and protein in the uncoated Ag-NPs, PVP-coated Ag-NPs, silver nitrate and sodium nitrate groups were all significantly decreased. The levels of GAP-43 mRNA and protein of rats in the uncoated Ag-NPs group was significantly lower than those in the later three groups, while there was no significant difference among the later three groups.Maternal exposure to uncoated Ag-NPs during pregnancy impaired spatial cognition in rat offspring. GAP-43 reduction might be involved in the cognitive impairment. The toxicity was mainly associated with release of silver ion. Coating with PVP reduced the toxicity of Ag-NPs.