Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, United States.
Healthcare Business Unit, Nikon Corporation, Tokyo, Japan.
eNeuro. 2018 Jun 29;5(3). doi: 10.1523/ENEURO.0001-18.2018. eCollection 2018 May-Jun.
Human neurons expressing mutations associated with neurodegenerative disease are becoming more widely available. Hence, developing assays capable of accurately detecting changes that occur early in the disease process and identifying therapeutics able to slow these changes should become ever more important. Using automated live-cell imaging, we studied human motor neurons in the process of dying following neurotrophic factor withdrawal. We tracked different neuronal features, including cell body size, neurite length, and number of nodes. In particular, measuring the number of nodes in individual neurons proved to be an accurate predictor of relative health. Importantly, intermediate phenotypes were defined and could be used to distinguish between agents that could fully restore neurons and neurites and those only capable of maintaining neuronal cell bodies. Application of live-cell imaging to disease modeling has the potential to uncover new classes of therapeutic molecules that intervene early in disease progression.
表达与神经退行性疾病相关突变的人类神经元正变得越来越普及。因此，开发能够准确检测疾病早期发生的变化并识别能够减缓这些变化的治疗方法应该变得越来越重要。我们使用自动化活细胞成像技术研究了神经营养因子耗尽后死亡的人类运动神经元。我们跟踪了不同的神经元特征，包括细胞体大小、轴突长度和节点数量。特别是，测量单个神经元中的节点数量被证明是预测相对健康状况的准确指标。重要的是，定义了中间表型，并可用于区分能够完全恢复神经元和轴突的试剂与仅能够维持神经元细胞体的试剂。将活细胞成像应用于疾病建模有可能发现新的治疗分子类别，这些分子类别能够在疾病进展的早期介入。
