Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain
Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain
复制标题
DOI：
10.3791/56014
复制
发表时间：
2017-10-01
影响因子：
1.2
通讯作者：
Kizil, Caghan
中科院分区：
文献类型：
--
作者：
Bhattarai, Prabesh;Thomas, Alvin Kuriakose;Kizil, Caghan
阿尔茨海默氏病（AD）是一种使人衰弱的神经退行性疾病，其中有毒淀粉样蛋白β42（β42）的肽会导致突触变性，炎症，神经元死亡和学习缺陷。在AD的情况下，人类无法再生神经元损失，部分原因是神经茎/祖细胞（NSPC）的增殖能力受损和神经发生降低。因此，有效的再生疗法还应增强NSPC的增殖和神经源能力。斑马鱼（Danio Rerio）是一种再生生物，我们可以学习基本的分子程序，可以通过这些程序来设计解决AD的治疗方法。因此，有必要在斑马鱼中产生类似广告的模型。使用我们的方法，我们可以引入具有组织渗透能力的β42肽的合成衍生物，并分析疾病病理学和再生反应。比现有方法或动物模型的优势在于斑马鱼可以教会我们如何自然再生，从而帮助我们通过靶向内源性NSPC来更好地治疗人类神经退行性疾病。因此，成人斑马鱼大脑中建立的淀粉样蛋白毒性模型可能为神经科学和临床医学领域的研究开辟新的途径。此外，这种方法的简单执行允许进行具有成本效益和有效的实验评估。该手稿描述了将β42肽的合成和注射到斑马鱼大脑中。
Alzheimer's disease (AD) is a debilitating neurodegenerative disease in which accumulation of toxic amyloid-beta 42 (A beta 42) 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 A beta 42 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 A beta 42 peptides into zebrafish brain.