Zhang Qinli, Ding Yong, He Kaihong, Li Huan, Gao Fuping, Moehling Taylor J, Wu Xiaohong, Duncan Jeremy, Niu Qiao
Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China.
Department of Pathology, University of Mississippi Medical Center, Jackson, MS, United States.
Front Pharmacol. 2018 Mar 20;9:253. doi: 10.3389/fphar.2018.00253. eCollection 2018.
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.
氧化铝纳米颗粒（AlNP）已被证明会在器官中蓄积并穿透生物屏障，从而在许多器官系统中产生毒性作用。然而，尚不清楚孕期雌性小鼠接触AlNP是否会影响中枢神经系统的发育或诱发后代的神经发育毒性。本研究旨在探讨AlNP对神经发育的影响及其相关潜在机制。将ICR品系成年雌性小鼠随机分为四组，在整个孕期分别用生理盐水（对照组）、粒径为10μm的氧化铝（块状Al）以及50nm和13nm的AlNP进行处理。测定新生小鼠海马体中的铝含量，并追踪后代从出生到1月龄的神经发育行为。此外，还测定了青春期小鼠大脑皮层中的氧化应激和神经递质水平。我们的结果表明，AlNP处理组新生小鼠海马体中的铝含量显著高于块状Al组和对照组。此外，AlNP处理的雌性小鼠所产后代表现出神经发育行为迟缓。最后，AlNP处理组小鼠的后代在1月龄时表现出焦虑样行为显著增加，学习和记忆能力受损。潜在机制可能与大脑皮层氧化应激增加和神经递质水平降低有关。因此，我们得出结论，孕期雌性小鼠接触AlNP可诱发后代的神经发育毒性。
