IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Part Fibre Toxicol. 2022 Mar 25;19(1):23. doi: 10.1186/s12989-022-00461-2.
There is an increasing concern about the neurotoxicity of engineered nanomaterials (NMs). To investigate the effects of subchronic oral exposures to SiO and CeO NMs on Alzheimer's disease (AD)-like pathology, 5xFAD transgenic mice and their C57BL/6J littermates were fed ad libitum for 3 or 14 weeks with control food pellets, or pellets dosed with these respective NMs at 0.1% or 1% (w/w). Behaviour effects were evaluated by X-maze, string suspension, balance beam and open field tests. Brains were analysed for plaque load, beta-amyloid peptide levels, markers of oxidative stress and neuroinflammation.
No marked behavioural impairments were observed in the mice exposed to SiO or CeO and neither treatment resulted in accelerated plaque formation, increased oxidative stress or inflammation. In contrast, the 5xFAD mice exposed to 1% CeO for 14 weeks showed significantly lower hippocampal Aβ plaque load and improved locomotor activity compared to the corresponding controls.
The findings from the present study suggest that long-term oral exposure to SiO or CeO NMs has no neurotoxic and AD-promoting effects. The reduced plaque burden observed in the mice following dietary CeO exposure warrants further investigation to establish the underlying mechanism, given the easy applicability of this administration method.
人们越来越关注工程纳米材料（NMs）的神经毒性。为了研究亚慢性口服暴露于 SiO 和 CeO NMs 对阿尔茨海默病（AD）样病理学的影响，5xFAD 转基因小鼠及其 C57BL/6J 同窝仔鼠自由进食对照食物丸或分别用 0.1%或 1%（w/w）浓度的这些纳米材料处理的食物丸 3 或 14 周。通过 X 迷宫、悬线、平衡木和旷场试验评估行为效应。分析大脑中的斑块负荷、β-淀粉样肽水平、氧化应激和神经炎症标志物。
暴露于 SiO 或 CeO 的小鼠没有明显的行为障碍，两种处理都没有加速斑块形成、增加氧化应激或炎症。相比之下，14 周暴露于 1% CeO 的 5xFAD 小鼠与相应对照组相比，海马 Aβ 斑块负荷显著降低，运动活性提高。
本研究的结果表明，长期口服暴露于 SiO 或 CeO NMs 没有神经毒性和促进 AD 的作用。膳食 CeO 暴露后观察到的斑块负担减少需要进一步研究以确定潜在机制，因为这种给药方法易于应用。
