Department of Biology and Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Nanoscale. 2015 Oct 7;7(37):15225-37. doi: 10.1039/c5nr03598h.
The adverse effects of nanoscale-alumina (Al2O3-NPs) have been previously demonstrated in both in vitro and in vivo studies, whereas little is known about their mechanism of neurotoxicity. It is the goal of this research to determine the toxic effects of nano-alumina on human neuroblastoma SH-SY5Y and mouse hippocampal HT22 cells in vitro and on ICR female mice in vivo. Nano-alumina displayed toxic effects on SH-SY5Y cell lines in three different concentrations also increased aluminium abundance and induced oxidative stress in HT22 cells. Nano-alumina peripherally administered to ICR female mice for three weeks increased brain aluminium and ROS production, disturbing brain energy homeostasis, and led to the impairment of hippocampus-dependent memory. Most importantly, these nano-particles induced Alzheimer disease (AD) neuropathology by enhancing the amyloidogenic pathway of Amyloid Beta (Aβ) production, aggregation and implied the progression of neurodegeneration in the cortex and hippocampus of these mice. In conclusion, these data demonstrate that nano-alumina is toxic to both cells and female mice and that prolonged exposure may heighten the chances of developing a neurodegenerative disease, such as AD.
纳米氧化铝(Al2O3-NPs)的不良影响已在前人的体外和体内研究中得到证实,而其神经毒性的机制知之甚少。本研究旨在确定纳米氧化铝对体外培养的人神经母细胞瘤 SH-SY5Y 和小鼠海马 HT22 细胞以及体内 ICR 雌性小鼠的毒性作用。纳米氧化铝在三种不同浓度下对 SH-SY5Y 细胞系表现出毒性作用,同时增加了铝的丰度,并诱导 HT22 细胞氧化应激。纳米氧化铝经外周给予 ICR 雌性小鼠 3 周,增加了大脑中的铝和 ROS 产生,扰乱了大脑能量平衡,导致海马依赖性记忆受损。最重要的是,这些纳米颗粒通过增强淀粉样蛋白β(Aβ)产生、聚集的淀粉样形成途径,诱导阿尔茨海默病(AD)神经病理学,并暗示这些小鼠大脑皮层和海马中的神经退行性变进展。总之,这些数据表明,纳米氧化铝对细胞和雌性小鼠均具有毒性,长期暴露可能会增加患神经退行性疾病(如 AD)的几率。