Abstract

High prevalence of human brain disorders necessitates development of the reliable peripheral biomarkers as diagnostic and disease-monitoring tools. In addition to clinical studies, animal models markedly advance studying of non-brain abnormalities associated with brain pathogenesis. The zebrafish (Danio rerio) is becoming increasingly popular as an animal model organism in translational neuroscience. These fish share some practical advantages over mammalian models together with high genetic homology and evolutionarily conserved biochemical and neurobehavioral phenotypes, thus enabling large-scale modeling of human brain diseases. Here, we review mounting evidence on peripheral biomarkers of brain disorders in zebrafish models, focusing on altered biochemistry (lipids, carbohydrates, proteins, and other non-signal molecules, as well as metabolic reactions and activity of enzymes). Collectively, these data strongly support the utility of zebrafish (from a systems biology standpoint) to study peripheral manifestations of brain disorders, as well as highlight potential applications of biochemical biomarkers in zebrafish models to biomarker-based drug discovery and development.

中文翻译：

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开发脑部疾病的外周生化生物标志物：来自斑马鱼模型的见解

摘要

人类大脑疾病的高患病率需要开发可靠的外周生物标志物作为诊断和疾病监测工具。除了临床研究之外，动物模型显着推进了与脑发病机制相关的非脑异常的研究。斑马鱼（Danio rerio）作为转化神经科学中的动物模型生物越来越受欢迎。这些鱼与哺乳动物模型相比具有一些实际优势，以及高度的遗传同源性和进化上保守的生化和神经行为表型，从而能够大规模模拟人脑疾病。在这里，我们回顾了斑马鱼模型中脑部疾病的外周生物标志物的越来越多的证据，重点关注生物化学的改变（脂质、碳水化合物、蛋白质和其他非信号分子，以及代谢反应和酶活性）。总的来说，这些数据有力地支持了斑马鱼（从系统生物学的角度）研究脑部疾病的外周表现的效用，并强调了斑马鱼模型中生化生物标志物在基于生物标志物的药物发现和开发中的潜在应用。