Department of Biomedical Science, Quillen College of Medicine, Eastern Tennessee State University, Box 70582, Johnson City, TN 37614-1708, United States.
Temasek Life Sciences Laboratory, 1 Research Link 117604, Singapore.
Curr Aging Sci. 2021;14(2):78-93. doi: 10.2174/1874609814666210202091301.
New models in which aging-related neurodegeneration more closely resembling the combination of pathologies that develop in aging humans, are needed. The fish Nothobranchius, which naturally develops such pathologies over the course of its short lifespan, is one such model. This review compares the lifespans and pathologies of different Nothobranchius strains to those of current vertebrate models of aging. Furthermore, existing data pertaining to neurodegeneration in these fish is discussed in the context of their reported neuropathologies, along with open questions related to mammalian chronopathologies. Specifically, the evidence for a Parkinson's disease-like pathology is discussed. Neurogenesis and age-related changes therein are discussed in the context of siRNA and neurodegeneration. We also discuss changes in the expression of neuropeptide Y in relation to the brain-gut axis and how these change with age. Age-related behavioral changes are discussed, along with the assays used in their evaluation. Genetic discoveries are outlined and discussed with a view on DJ-1/NRF2 signaling in N. furzeri, and insights gained from comparative genomics and siRNA studies. Finally, research focus areas are highlighted, and a case is made for the utility of these fish in the study of aging-related neurodegeneration, and to screen for environmental risk factors of aging-related neuropathology.
需要新的模型来更紧密地模拟与衰老相关的神经退行性变，这些模型更类似于在衰老人类中发展的多种病理学的组合。自然会在其短暂的寿命过程中发展出此类病理学的鱼类非洲鲫鱼就是这样的一种模型。本文将不同的非洲鲫鱼品系的寿命和病理学与当前衰老的脊椎动物模型进行了比较。此外，还根据这些鱼类报道的神经病理学，以及与哺乳动物 chronopathologies 相关的开放性问题，讨论了有关这些鱼类神经退行性变的现有数据。具体而言，讨论了类似于帕金森病的病理学的证据。在 siRNA 的背景下讨论了神经发生及其与年龄相关的变化和神经退行性变。我们还讨论了与脑肠轴相关的神经肽 Y 表达的变化以及这些变化如何随年龄而变化。讨论了与年龄相关的行为变化，以及评估这些变化所使用的测定方法。概述了遗传发现，并讨论了 N. furzeri 中的 DJ-1/NRF2 信号，以及从比较基因组学和 siRNA 研究中获得的见解。最后，突出了研究重点领域，并提出了这些鱼类在研究与衰老相关的神经退行性变以及筛选与衰老相关的神经病理学的环境风险因素中的应用。
