Abstract
Alumina nanoparticles (AlNP) have been shown to accumulate in organs and penetrate biological barriers which lead to toxic effects in many organ systems. However, it is not known whether AlNP exposure to female mice during pregnancy can affect the development of the central nervous system or induce neurodevelopmental toxicity in the offspring. The present study aims to examine the effect of AlNP on neurodevelopment and associated underlying mechanism. ICR strain adult female mice were randomly divided into four groups, which were treated with normal saline (control), 10 μm particle size of alumina (bulk-Al), and 50 and 13 nm AlNP during entire pregnancy period. Aluminum contents in the hippocampus of newborns were measured and neurodevelopmental behaviors were tracked in the offspring from birth to 1 month of age. Furthermore, oxidative stress and neurotransmitter levels were measured in the cerebral cortex of the adolescents. Our results showed that aluminum contents in the hippocampus of newborns in AlNP-treated groups were significantly higher than those in bulk-Al and controls. Moreover, the offspring delivered by AlNP-treated female mice displayed stunted neurodevelopmental behaviors. Finally, the offspring of AlNP-treated mice demonstrated significantly increased anxiety-like behavior with impaired learning and memory performance at 1 month of age. The underlying mechanism could be related to increased oxidative stress and decreased neurotransmitter levels in the cerebral cortex. We therefore conclude that AlNP exposure of female mice during pregnancy can induce neurodevelopmental toxicity in offspring.
Highlights
Neurodevelopmental disabilities affect millions of children worldwide (Grandjean and Landrigan, 2014); it is mainly because the placenta does not block the transmission of many environmental toxicants from the maternal to the fetal circulation (Needham et al, 2011)
The newborn pups delivered by Alumina nanoparticles (AlNP)-treated mice had significantly lower Body weight (BW) on PD1 compared with controls [F(3,188) = 30.14, p < 0.0001; Figure 3A]
There was a significant decrease in the birth weight of pups delivered by female mice treated with both 50 and 13 nm AlNP compared with those treated with bulk alumina (bulk-Al) and normal saline controls
Summary
Neurodevelopmental disabilities affect millions of children worldwide (Grandjean and Landrigan, 2014); it is mainly because the placenta does not block the transmission of many environmental toxicants from the maternal to the fetal circulation (Needham et al, 2011). Studies have shown that AlNP can penetrate biological barriers and accumulate in multiple organs (Chen et al, 2008; Oesterling et al, 2008; Almeida et al, 2011; Morsy et al, 2016b), leading to neurotoxicity (Oesterling et al, 2008; Dong et al, 2011; Zhang et al, 2011; Chen et al, 2013; Shah et al, 2015; Morsy et al, 2016a), immunotoxicity (Braydich-Stolle et al, 2010), genotoxicity (Balasubramanyam et al, 2009a,b), as well as toxicity in the lung (Balasubramanyam et al, 2009a; Li et al, 2016), liver (Shrivastava et al, 2014; Morsy et al, 2016a), kidney (Morsy et al, 2016a), and skin (Dey et al, 2008). No studies have addressed whether AlNP induces developmental toxicity, and in particular, neurodevelopmental toxicity
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