Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str., 02-106 Warsaw, Poland.
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodźki str., 20-093 Lublin, Poland.
Ecotoxicol Environ Saf. 2021 Jan 15;208:111416. doi: 10.1016/j.ecoenv.2020.111416. Epub 2020 Oct 16.
The increasing production and use of silver nanoparticles (AgNPs) as antimicrobial agents in medicinal and commercial products creates a substantial risk of exposure, especially for infants and children. Our current knowledge concerning the impact of AgNPs on developing brain is insufficient. Therefore we investigated the temporal profile of transcriptional changes in cellular components of the neurovascular unit in immature rats exposed to a low dose of AgNPs. The behavior of animals under these conditions was also monitored. Significant deposition of AgNPs in brain of exposed rats was identified and found to persist over the post-exposure time. Substantial changes were noted in the transcriptional profile of tight junction proteins such as occludin and claudin-5, and pericyte-related molecules such as angiopoietin-1. Moreover, downregulation of platelet-derived growth factor (PDGFβ) and its receptor (PDGFβR) which constitute the main signaling pathway between endothelial cells and pericytes was observed. These were long-lasting effects, accompanied by overexpression of astroglial-specific GFAP mRNA and endothelial cell adhesion molecule, ICAM-1, involved in the pathomechanism of neuroinflammation. The profile of changes indicates that even low doses of AgNPs administered during the early stage of life induce dysregulation of neurovascular unit constituents which may lead to disintegration of the blood-brain barrier. This was confirmed by ultrastructural analysis that revealed enhanced permeability of cerebral microvessels resulting in perivascular edema. Changes in the behavior of exposed rats indicating pro-depressive and anti-anxiety impacts were also identified. The results show a high risk of using AgNPs in medical and consumer products dedicated for infants and children.
银纳米粒子（AgNPs）作为医药和商业产品中的抗菌剂，其产量和使用不断增加，这会大大增加暴露的风险，尤其是对婴儿和儿童而言。我们目前对于 AgNPs 对发育中大脑的影响知之甚少。因此，我们研究了暴露于低剂量 AgNPs 的未成熟大鼠神经血管单元细胞成分的转录变化的时程。同时还监测了这些条件下动物的行为。结果发现，暴露于 AgNPs 的大鼠的大脑中有大量 AgNPs 沉积，并且在暴露后时间内持续存在。紧密连接蛋白（如 occludin 和 claudin-5）和周细胞相关分子（如血管生成素-1）的转录谱发生了显著变化。此外，还观察到血小板衍生生长因子（PDGFβ）及其受体（PDGFβR）的下调，它们构成了内皮细胞和周细胞之间的主要信号通路。这些是持久的效应，伴随着星形胶质细胞特异性 GFAP mRNA 和内皮细胞黏附分子 ICAM-1 的过表达，它们参与了神经炎症的发病机制。这些变化表明，即使在生命早期给予低剂量的 AgNPs，也会导致神经血管单元成分的失调，从而可能导致血脑屏障的破坏。这通过超微结构分析得到了证实，该分析显示脑微血管的通透性增强，导致血管周围水肿。还发现了暴露于 AgNPs 的大鼠行为的变化，表明其具有促抑郁和抗焦虑的影响。研究结果表明，在专为婴儿和儿童设计的医疗和消费品中使用 AgNPs 存在高风险。
