Human-derived neurons and brain organoids have revolutionized our ability to model brain development in a dish. In this review, we discuss the potential for human brain models to advance drug discovery for complex neuropsychiatric disorders. First, we address the advantages of human brain models to screen for new drugs capable of altering CNS activity. Next, we propose an experimental pipeline for using human-derived neurons and brain organoids to rapidly assess drug impact on key events in brain development, including neurite extension, synapse formation, and neural activity. The experimental pipeline begins with automated high content imaging for analysis of neurites, synapses, and neuronal viability. Following morphological examination, multi-well microelectrode array technology examines neural activity in response to drug treatment. These techniques can be combined with high throughput sequencing and mass spectrometry to assess associated transcriptional and proteomic changes. These combined technologies provide a foundation for neuropsychiatric drug discovery and future clinical assessment of patient-specific drug responses.

中文翻译：

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人类衍生的大脑模型：进入神经精神疾病和药物疗法的窗口。

人类来源的神经元和脑类器官彻底改变了我们在盘子中模拟大脑发育的能力。在这篇综述中，我们讨论了人脑模型促进复杂神经精神疾病药物开发的潜力。首先，我们解决人脑模型的优势，以筛选能够改变CNS活性的新药。接下来，我们提出了一条使用人源性神经元和脑类器官来快速评估药物对大脑发育关键事件（包括神经突延伸，突触形成和神经活动）的影响的实验管道。实验流程从自动化的高内涵成像开始，用于神经突，突触和神经元活力的分析。经过形态学检查后，多孔微电极阵列技术检查了响应药物治疗的神经活动。这些技术可以与高通量测序和质谱相结合，以评估相关的转录和蛋白质组学变化。这些组合技术为神经精神药物发现和对患者特异性药物反应的未来临床评估提供了基础。