Rosca Andreea, Coronel Raquel, Moreno Miryam, González Rosa, Oniga Andreea, Martín Alberto, López Victoria, González María Del Carmen, Liste Isabel
Unidad de Regeneración Neural, Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC), Instituto de Salud Carlos III, Madrid, Spain.
Toxicología Ambiental, Centro Nacional de Sanidad Ambiental, Instituto de Salud Carlos III, Madrid, Spain.
Heliyon. 2020 Dec 19;6(12):e05773. doi: 10.1016/j.heliyon.2020.e05773. eCollection 2020 Dec.
The development of central nervous system is a highly coordinated and complex process. Any alteration of this process can lead to disturbances in the structure and function of the brain, which can cause deficits in neurological development, resulting in neurodevelopmental disorders, including, for example, autism or attention-deficit hyperactivity disorder. Exposure to certain chemicals during the fetal period and childhood is known to cause developmental neurotoxicity and has serious consequences that persist into adult life. For regulatory purposes, determination of the potential for developmental neurotoxicity is performed according the OECD Guideline 426, in which the test substance is administered to animals during gestation and lactation. However, these animal models are expensive, long-time consuming and may not reflect the physiology in humans; that makes it an unsustainable model to test the large amount of existing chemical products, hence alternative models to the use of animals are needed. One of the most promising methods is based on the use of stem cell technology. Stem cells are undifferentiated cells with the ability to self-renew and differentiate into more specialized cell types. Because of these properties, these cells have gained increased attention as possible therapeutic agents or as disease models. Here, we provide an overview of the current models both animal and cellular, available to study developmental neurotoxicity and review in more detail the usefulness of human stem cells, their properties and how they are becoming an alternative to evaluate and study the mechanisms of action of different environmental toxicants.
中枢神经系统的发育是一个高度协调且复杂的过程。这一过程的任何改变都可能导致大脑结构和功能的紊乱，进而引发神经发育缺陷，导致神经发育障碍，例如自闭症或注意力缺陷多动障碍。已知在胎儿期和儿童期接触某些化学物质会导致发育性神经毒性，并产生持续至成年期的严重后果。出于监管目的，根据经合组织准则426来确定发育性神经毒性的可能性，该准则要求在妊娠和哺乳期给动物施用受试物质。然而，这些动物模型成本高昂、耗时长久，且可能无法反映人类的生理情况；这使得它成为测试大量现有化学产品的不可持续模型，因此需要动物使用的替代模型。最有前景的方法之一是基于干细胞技术的应用。干细胞是未分化的细胞，具有自我更新和分化为更特化细胞类型的能力。由于这些特性，这些细胞作为可能的治疗剂或疾病模型受到了越来越多的关注。在此，我们概述了目前可用于研究发育性神经毒性的动物和细胞模型，并更详细地回顾了人类干细胞的实用性、它们的特性以及它们如何成为评估和研究不同环境毒物作用机制的替代方法。
