Experimental Medicine Program, University of British Columbia, 2329 West Mall, Vancouver, British Columbia, V6T 1Z4, Canada.
Experimental Medicine Program, University of British Columbia, 2329 West Mall, Vancouver, British Columbia, V6T 1Z4, Canada; Department of Ophthalmology and Visual Sciences, University of British Columbia, 2329 West Mall, Vancouver, British Columbia, V6T 1Z4, Canada.
Micron. 2020 Jun;133:102852. doi: 10.1016/j.micron.2020.102852. Epub 2020 Feb 20.
Many different types of pathologies can arise in the central nervous system (CNS), such as neurodegeneration. The incidence of neurodegenerative diseases continues to increase, yet the pathogenesis underlying most neurodegenerative diseases, notably in amyotrophic lateral sclerosis (ALS), remains elusive. Neuronal support cells, or glia, are known to play a crucial role in ALS. Microglia are the resident immune cells of the CNS and also have neurotrophic support functions. These cells have a disease-modifying function in ALS, yet this role is not well understood. A likely reason for this is that the intact CNS is particularly challenging to access for investigation in patients and in most animal models, which has impeded research in this field. The zebrafish is emerging as a robust model system to investigate cells in vivo, and offer distinct advantages over other vertebrate models for investigating neurodegenerative diseases. Live imaging in vivo is a powerful technique to characterize the role of dynamic cells such as microglia during neurodegeneration, and zebrafish provide a convenient means for live imaging. Here, we discuss the zebrafish as a model for live imaging, provide a brief overview of available high resolution imaging platforms that accommodate zebrafish, and describe our own in vivo studies on the role of microglia during motor neuron degeneration. Live in vivo imaging is anticipated to provide invaluable advancements to defining the pathogenesis underlying neurodegenerative diseases, which may in turn allow for more specifically targeted therapeutics.
许多不同类型的病理学可以出现在中枢神经系统（CNS）中，如神经退行性变。神经退行性疾病的发病率持续增加，但大多数神经退行性疾病的发病机制，尤其是肌萎缩侧索硬化症（ALS）的发病机制仍不清楚。神经元支持细胞，即神经胶质细胞，已知在 ALS 中发挥关键作用。小胶质细胞是中枢神经系统的固有免疫细胞，也具有神经营养支持功能。这些细胞在 ALS 中具有疾病修饰功能，但这一作用尚未得到很好的理解。造成这种情况的一个可能原因是，完整的中枢神经系统特别难以在患者和大多数动物模型中进行研究，这阻碍了该领域的研究。斑马鱼正在成为一种强大的体内细胞研究模型系统，并且在研究神经退行性疾病方面优于其他脊椎动物模型。体内实时成像技术是研究神经退行性变过程中动态细胞（如小胶质细胞）作用的有力手段，而斑马鱼为体内实时成像提供了便利的手段。在这里，我们讨论了斑马鱼作为活体成像模型，简要概述了可容纳斑马鱼的现有高分辨率成像平台，并描述了我们自己在活体研究小胶质细胞在运动神经元退化中的作用。活体实时成像有望为定义神经退行性疾病的发病机制提供宝贵的进展，这反过来可能允许更有针对性的治疗方法。
