Bhattarai Prabesh, Thomas Alvin Kuriakose, Cosacak Mehmet Ilyas, Papadimitriou Christos, Mashkaryan Violeta, Zhang Yixin, Kizil Caghan
German Centre for Neurodegenerative Diseases (DZNE) Dresden within Helmholtz Association.
B CUBE, Center for Molecular Bioengineering, Technische Universität Dresden.
J Vis Exp. 2017 Oct 25(128):56014. doi: 10.3791/56014.
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-β42 (Aβ42) peptides leads to synaptic degeneration, inflammation, neuronal death, and learning deficits. Humans cannot regenerate lost neurons in the case of AD in part due to impaired proliferative capacity of the neural stem/progenitor cells (NSPCs) and reduced neurogenesis. Therefore, efficient regenerative therapies should also enhance the proliferation and neurogenic capacity of NSPCs. Zebrafish (Danio rerio) is a regenerative organism, and we can learn the basic molecular programs with which we could design therapeutic approaches to tackle AD. For this reason, the generation of an AD-like model in zebrafish was necessary. Using our methodology, we can introduce synthetic derivatives of Aβ42 peptide with tissue penetrating capability into the adult zebrafish brain, and analyze the disease pathology and the regenerative response. The advantage over the existing methods or animal models is that zebrafish can teach us how a vertebrate brain can naturally regenerate, and thus help us to treat human neurodegenerative diseases better by targeting endogenous NSPCs. Therefore, the amyloid-toxicity model established in the adult zebrafish brain may open new avenues for research in the field of neuroscience and clinical medicine. Additionally, the simple execution of this method allows for cost-effective and efficient experimental assessment. This manuscript describes the synthesis and injection of Aβ42 peptides into zebrafish brain.
阿尔茨海默病（AD）是一种使人衰弱的神经退行性疾病，其中有毒的淀粉样β42（Aβ42）肽的积累会导致突触退化、炎症、神经元死亡和学习缺陷。在AD情况下，人类无法再生失去的神经元，部分原因是神经干/祖细胞（NSPCs）的增殖能力受损以及神经发生减少。因此，有效的再生疗法还应增强NSPCs的增殖和神经发生能力。斑马鱼（Danio rerio）是一种具有再生能力的生物，我们可以从中了解基本的分子程序，据此设计治疗AD的方法。因此，有必要在斑马鱼中建立类似AD的模型。使用我们的方法，我们可以将具有组织穿透能力的Aβ42肽合成衍生物引入成年斑马鱼大脑，并分析疾病病理学和再生反应。与现有方法或动物模型相比，优势在于斑马鱼可以让我们了解脊椎动物大脑如何自然再生，从而通过靶向内源性NSPCs帮助我们更好地治疗人类神经退行性疾病。因此，在成年斑马鱼大脑中建立的淀粉样毒性模型可能为神经科学和临床医学领域的研究开辟新途径。此外，该方法操作简单，可进行经济高效的实验评估。本文描述了Aβ42肽的合成及其向斑马鱼大脑中的注射。
