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Investigating microglia during motor neuron degeneration using a zebrafish model
Micron ( IF 2.5 ) Pub Date : 2020-02-20 , DOI: 10.1016/j.micron.2020.102852
Jessica R. Morrice , Cheryl Y. Gregory-Evans , Christopher A. Shaw

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.



中文翻译:

使用斑马鱼模型调查运动神经元变性期间的小胶质细胞

中枢神经系统(CNS)可能会出现许多不同类型的病理,例如神经变性。神经退行性疾病的发病率继续增加,但是大多数神经退行性疾病的发病机制,尤其是在肌萎缩性侧索硬化症(ALS)中,仍然难以捉摸。已知神经元支持细胞或神经胶质在ALS中起关键作用。小胶质细胞是中枢神经系统的固有免疫细胞,还具有神经营养支持功能。这些细胞在ALS中具有缓解疾病的功能,但这种作用尚不十分清楚。造成这种情况的可能原因是,完整的中枢神经系统特别难以进入患者和大多数动物模型的研究范围,这阻碍了该领域的研究。斑马鱼正在成为研究体内细胞的强大模型系统,并且在研究神经退行性疾病方面比其他脊椎动物模型具有明显优势。体内实时成像是一种强大的技术,可表征神经变性期间动态细胞(例如小胶质细胞)的作用,而斑马鱼为实时成像提供了便捷的方法。在这里,我们讨论斑马鱼作为实时成像的模型,简要概述适用斑马鱼的高分辨率成像平台,并描述我们自己的关于小胶质细胞在运动神经元变性中的作用的体内研究。活体内成像预计将提供宝贵的进步到限定发病的神经变性疾病,其可以反过来允许更具体地靶向治疗剂的下面。

更新日期:2020-02-20
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