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Advancing preclinical models of psychiatric disorders with human brain organoid cultures
Molecular Psychiatry ( IF 11.0 ) Pub Date : 2022-08-10 , DOI: 10.1038/s41380-022-01708-2
Thomas Anthony Dixon 1 , Alysson R Muotri 2
Affiliation  

Psychiatric disorders are often distinguished from neurological disorders in that the former do not have characteristic lesions or findings from cerebrospinal fluid, electroencephalograms (EEGs), or brain imaging, and furthermore do not have commonly recognized convergent mechanisms. Psychiatric disorders commonly involve clinical diagnosis of phenotypic behavioral disturbances of mood and psychosis, often with a poorly understood contribution of environmental factors. As such, psychiatric disease has been challenging to model preclinically for mechanistic understanding and pharmaceutical development. This review compares commonly used animal paradigms of preclinical testing with evolving techniques of induced pluripotent cell culture with a focus on emerging three-dimensional models. Advances in complexity of 3D cultures, recapitulating electrical activity in utero, and disease modeling of psychosis, mood, and environmentally induced disorders are reviewed. Insights from these rapidly expanding technologies are discussed as they pertain to the utility of human organoid and other models in finding novel research directions, validating pharmaceutical action, and recapitulating human disease.



中文翻译:

用人脑类器官培养推进精神疾病的临床前模型

精神疾病通常与神经系统疾病不同,因为前者没有特征性病变或脑脊液、脑电图 (EEG) 或脑成像的发现,而且没有公认的收敛机制。精神疾病通常涉及情绪表型行为障碍和精神病的临床诊断,通常对环境因素的贡献知之甚少。因此,精神疾病在临床前建模以了解机制和药物开发一直具有挑战性。这篇综述比较了临床前测试的常用动物范例与诱导多能细胞培养的不断发展的技术,重点是新兴的三维模型。3D 培养复杂性的进步,回顾了子宫内的电活动,以及精神病、情绪和环境诱发的疾病的疾病模型。讨论了这些快速发展的技术的见解,因为它们与人类类器官和其他模型在寻找新研究方向、验证药物作用和重现人类疾病方面的效用有关。

更新日期:2022-08-10
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