Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, Anton Guenther-Strasse 51, 72488, Sigmaringen, Germany.
Department of Biology, University of Konstanz, Universitaetstrasse 10, 78467, Konstanz, Germany.
Arch Toxicol. 2019 Oct;93(10):2879-2893. doi: 10.1007/s00204-019-02553-z. Epub 2019 Sep 7.
Prenatal brain development is a complex and sensitive process, highly susceptible to environmental influences such as pollutants, stress, malnutrition, drugs, tobacco exposure, or ionizing radiation (IR). Disturbances in development may cause life-long disabilities and diseases, such as ADHD, childhood cancers, cognitive problems, depression, anxiety and more severe developmental disabilities. Due to increasing medical imaging, radiation therapy, natural terrestrial radiation, radioactive pollution and long-distance flights, humans are increasingly exposed to IR. However, data on impact of IR on very early human brain development are scarce, particularly in the very first weeks of gestation. Here we investigated the effects of low-dose X-ray IR (1 Gy) in a 3D early brain developmental model derived from human pluripotent stem cells. In this model very early neural stem cells, neuroectodermal progenitor cells (NEP), were exposed to low-dose IR and direct as well as delayed effects were investigated. Expression of 20 different marker genes crucial for normal neural development was determined 48 h and 9 days post IR (pIR). All but one of the analyzed marker genes were reduced 48 h after IR, and all but seven genes normalized their expression by day 9 pIR. Among the seven markers were genes involved in neurodevelopmental and growth abnormalities. Moreover, we could show that stemness of the NEP was reduced after IR. We were thus able to identify a significant impact of radiation in cells surviving low-dose IR, suggesting that low-dose IR could have a negative impact on the early developing human brain, with potential later detrimental effects.
产前大脑发育是一个复杂而敏感的过程，极易受到环境因素的影响，如污染物、压力、营养不良、药物、烟草暴露或电离辐射（IR）。发育过程中的干扰可能导致终身残疾和疾病，如注意力缺陷多动障碍、儿童癌症、认知问题、抑郁、焦虑以及更严重的发育障碍。由于医疗成像、放射治疗、天然陆地辐射、放射性污染和长途飞行的增加，人类接触 IR 的风险越来越大。然而，关于 IR 对人类早期大脑发育影响的数据仍然很少，特别是在妊娠的最初几周。在这里，我们使用源自人类多能干细胞的 3D 早期大脑发育模型研究了低剂量 X 射线 IR（1 Gy）的影响。在该模型中，早期神经干细胞和神经外胚层祖细胞（NEP）暴露于低剂量 IR 中，并研究了直接和延迟的影响。在 IR 后 48 小时和 9 天（pIR）测定了 20 个对正常神经发育至关重要的不同标记基因的表达。除了一个之外，所有分析的标记基因在 IR 后 48 小时都减少了，并且所有基因在 pIR 第 9 天都恢复了正常表达。这七个标记基因中有七个与神经发育和生长异常有关。此外，我们还证明了 IR 后 NEP 的干性降低。因此，我们能够确定辐射对存活于低剂量 IR 中的细胞有显著影响，这表明低剂量 IR 可能对早期发育中的人类大脑有负面影响，从而产生潜在的后期有害影响。
