Neurodegenerative diseases are complex and progressive, posing challenges to their study and understanding. Recent advances in microscopy imaging technologies have enabled the exploration of neurons in three spatial dimensions (3D) over time (4D). When applied to 3D cultures, tissues, or animals, these technologies can provide valuable insights into the dynamic and spatial nature of neurodegenerative diseases. This review focuses on the use of imaging techniques and neurodegenerative disease models to study neurodegeneration in 4D. Imaging techniques such as confocal microscopy, two-photon microscopy, miniscope imaging, light sheet microscopy, and robotic microscopy offer powerful tools to visualize and analyze neuronal changes over time in 3D tissue. Application of these technologies to models of neurodegeneration such as mouse organotypic culture systems and human organoid models provide versatile platforms to study neurodegeneration in a physiologically relevant context. Additionally, use of 4D imaging , including in mouse and zebrafish models of neurodegenerative diseases, allows for the investigation of early dysfunction and behavioral changes associated with neurodegeneration. We propose that these studies have the power to overcome the limitations of two-dimensional monolayer neuronal cultures and pave the way for improved understanding of the dynamics of neurodegenerative diseases and the development of effective therapeutic strategies.

中文翻译：

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三维和四维实时成像研究进行性神经变性的机制


神经退行性疾病是复杂且进行性的，对他们的研究和理解提出了挑战。显微成像技术的最新进展使得随着时间的推移 (4D) 在三个空间维度 (3D) 中探索神经元成为可能。当应用于 3D 培养物、组织或动物时，这些技术可以为神经退行性疾病的动态和空间性质提供有价值的见解。本综述重点关注使用成像技术和神经退行性疾病模型来研究 4D 神经退行性疾病。共焦显微镜、双光子显微镜、微型显微镜成像、光片显微镜和机器人显微镜等成像技术提供了强大的工具来可视化和分析 3D 组织中神经元随时间的变化。将这些技术应用于神经变性模型，例如小鼠器官培养系统和人类类器官模型，为在生理相关背景下研究神经变性提供了通用平台。此外，使用 4D 成像（包括在神经退行性疾病的小鼠和斑马鱼模型中）可以研究与神经退行性疾病相关的早期功能障碍和行为变化。我们认为这些研究有能力克服二维单层神经元培养的局限性，并为更好地了解神经退行性疾病的动力学和开发有效的治疗策略铺平道路。