Induced adverse effects of prenatal exposure to silver nanoparticles on neurobehavioral development of offspring of mice

Abstract

Steadily increased use of silver nanoparticles (Ag-NPs), has increased the amount of its exposure to humans and animals. Current scarce knowledge about the influences of prenatal exposure to Ag-NPs on postnatal outcomes, motivated us to investigate whether being exposed to it during pregnancy has any effects on neurobehavioral development of the adult offspring. Thirty virgin female NMRI mice were mated and treated subcutaneously once every three days from gestation day 3 until delivery, by 0, 0.2 and 2 mg/kg of bodyweight (BW) of Ag-NPs. Behavioral functions of adult offspring including spatial memory, passive avoidance learning, stress, anxiety-like behaviors and locomotor activities were assessed by commonly used neurobehavioral paradigms and the results were compared according to treatment and sex. Prenatal exposure to Ag-NPs significantly impaired their cognitive behavior in the Morris water maze. Although no evidence was observed indicating more anxiety-like behaviors in the treated offspring in the elevated plus maze, the number of defecations and leanings in the open field assay and number of passages in the light-dark box were greater in groups prenatally treated by Ag-NPs. Most of the impairments were more apparent in the offspring which had been prenatally exposed to high doses of Ag-NPs, particularly female ones. The present study indicated that the exposure of pregnant animals to Ag-NPs may lead to various neurobehavioral disorders in their offspring. Thus, more attention should be paid to avoid exposure to Ag-NPs, especially from pregnant females.

Effects of developmental exposure to silver in ionic and nanoparticle form: A study in rats

“…Coating with PVP protected offspring from the toxic effects of Ag-NPs in that study [ 45 ]. Ghaderi et al reported that subcutaneous injection of Ag-NPs during pregnancy could induce adverse consequences on neurobehavioral development of offspring because of its damage on spatial cognition [ 17 ].…”

“…The authors argued that this finding might be due to facilitation of aggregates at higher gut concentrations, preventing internalization via the gastrointestinal tract and thereby reducing fetotoxicity at higher doses [ 16 ]. The potential negative effects of Ag NPs on development and reproduction have yet to be fully clarified [ 17 ]. In comparison, only one rodent study has investigated the developmental toxicity of orally administered ionic silver (190 mg kg/day) on gestational day 1–20.…”

Disposition of intravenously or orally administered silver nanoparticles in pregnant rats and the effect on the biochemical profile in urine

“…It is important to remember that the placenta is not just a filter protecting the developing fetus from maternal blood substances, but also plays an important role in, for example, in fetal brain development (Bonnin and Levitt, 2012;Hsiao and Patterson, 2012;Zeltser and Leibel, 2011). The internal concentration of silver in the placenta might point to the mechanisms behind the reported impact on fetal brain and neurological development after prenatal AgNP exposure (Lale Ataei and Ebrahimzadeh-bideskan, 2014;Ganjuri et al, 2015;Ghaderi et al, 2015;Wu et al, 2015). Circulating biomarkers like selected pro-and anti-inflammatory cytokines and chemokines were analyzed in the plasma of pregnant rats to understand possible correlations with nanosilver exposure.…”

“…Wu and colleagues also found that offspring at postnatal day 35 performed less well in the Morris Water Maze, suggesting impaired spatial cognition in rat offspring following prenatal exposure (Wu, et al 2015). Postnatal neurobehavioral disorders as a resulting from prenatal exposure to AgNP has also been reported in mice (Ghaderi, et al 2015). …”

Gut Dysbiosis and Neurobehavioral Alterations in Rats Exposed to Silver Nanoparticles

“…In vitro and in vivo studies also suggest that AgNPs can induce transcriptomic and non-coding RNA changes in neuronal cells and various brain regions, especially the hippocampus [12][13][14][15][16][17][18][19][20] . Behavioral disruptions, especially in cognitive functions, potential anxiogenic effects, depression-like behaviors, and altered activity levels, have been reported after direct or developmental exposure of rodents and zebrafish to AgNPs 12,13,[21][22][23][24][25] . Other observed neurotoxicological effects include increased permeability of the blood-brain-barrier (BBB), edema formation, neuronal degradation and apoptosis, synaptic degeneration, tight junction disruptions, increase in reactive oxygen species (ROS), amyloid-β (Aβ) plagues, and astrocyte swelling 15-18, 20, 22, 23, 26-31 .…”