类脑器官在环境毒理学中的应用

Application of brain organoids in environmental toxicology

自19世纪以来,模式生物的出现帮助研究人员进一步了解细胞信号通路,确定药物靶点以及进行环境毒理学的研究。外源性化学物质,如污染物、药物和工业化学品,可能会影响大脑的生物过程或其功能,并最终导致神经疾病。然而人脑是一个复杂的、组织严密的器官,在很多方面与模式生物有着根本的区别。由于物种的差异,动物模型可能不能完全的模拟人脑以测试环境污染物的神经毒性。由人多能干细胞诱导而来的人类脑器官在基因组、转录组以及代谢组水平更贴合人体的真实情况,提供了测试以及预测环境污染物神经毒性的有效平台,成为研究神经毒理学的新模型。本文综述了类脑器官技术的新进展及其在评估环境毒物方面的应用,以期为类脑器官在环境神经毒理学应用提供新见解。

Since the 19th century,the emergence of model systems has helped researchers further understand cellular signaling pathways,identify potential drug targets,and conduct environmental toxicological studies.Exogenous chemicals,such as pollutants,drugs,and industrial chemicals,may affect brain biological processes and functions and eventually lead to neurological diseases.However,the brain is a complex and well-organized human organ,which is fundamentally different from any existing model system.Animal models may not be able to completely simulate the human brain in testing the neurotoxicity of environmental pollutants due to species differences.Human brain organoids,generated from human pluripotent stem cells,are emerging model systems for neurotoxicological research in line with the real situation of human body at the level of genome,transcriptome,and metabolome,and provide an effective platform for testing neurotoxicity of environmental toxins.We reviewed the latest development of brain organoids technology and its application in the evaluation of environmental neurotoxins,and provided new insights into the application of brain organoids in environmental neurotoxicology.