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Zebrafish drug screen

Christopher J Lambert, Briana C Freshner, Arlen Chung, Tamara J Stevenson, D Miranda Bowles, Raheel Samuel, Bruce K Gale, Joshua L Bonkowsky
Zebrafish are a valuable model organism in biomedical research. Their rapid development, ability to model human diseases, utility for testing genetic variants identified from next-generation sequencing, amenity to CRISPR mutagenesis, and potential for therapeutic compound screening, has led to their wide-spread adoption in diverse fields of study. However, their power for large-scale screens is limited by the absence of automated genotyping tools for live animals. This constrains potential drug screen options, limits analysis of embryonic and larval phenotypes, and requires raising additional animals to adulthood to ensure obtaining an animal of the desired genotype...
2018: PloS One
Rita Fior, Miguel Godinho Ferreira
No abstract text is available yet for this article.
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Peter J Steenbergen
BACKGROUND: Zebrafish larvae have a high potential as model system to replace rodents, especially in screening and drug discovery applications. However, an experimental setup to deliver mild electrical stimuli with simultaneous high throughput behavioural tracking has not yet been described. NEW METHOD: A new tool was designed, making the delivery of electrical stimuli in a 96-well plate format possible. Using custom made electrode clips that can be slid over the walls of a square 96-well plate, 80 larvae could be tested simultaneously and behavioural responses recorded...
March 6, 2018: Journal of Neuroscience Methods
Jing Shen, Sara Najafi, Sina Stäble, Johannes Fabian, Emily Koeneke, Fiona R Kolbinger, Jagoda K Wrobel, Benjamin Meder, Martin Distel, Tino Heimburg, Wolfgang Sippl, Manfred Jung, Heike Peterziel, Dominique Kranz, Michael Boutros, Frank Westermann, Olaf Witt, Ina Oehme
The prognosis of advanced stage neuroblastoma patients remains poor and, despite intensive therapy, the 5-year survival rate remains less than 50%. We previously identified histone deacetylase (HDAC) 8 as an indicator of poor clinical outcome and a selective drug target for differentiation therapy in vitro and in vivo. Here, we performed kinome-wide RNAi screening to identify genes that are synthetically lethal with HDAC8 inhibitors. These experiments identified the neuroblastoma predisposition gene ALK as a candidate gene...
March 7, 2018: Cell Death and Differentiation
Tal Teitz, Jie Fang, Asli N Goktug, Justine D Bonga, Shiyong Diao, Robert A Hazlitt, Luigi Iconaru, Marie Morfouace, Duane Currier, Yinmei Zhou, Robyn A Umans, Michael R Taylor, Cheng Cheng, Jaeki Min, Burgess Freeman, Junmin Peng, Martine F Roussel, Richard Kriwacki, R Kiplin Guy, Taosheng Chen, Jian Zuo
Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration-approved drugs to prevent or treat it. We screened 4,385 small molecules in a cochlear cell line and identified 10 compounds that protected against cisplatin toxicity in mouse cochlear explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), protected zebrafish lateral-line neuromasts from cisplatin toxicity and, when delivered locally, protected adult mice and rats against cisplatin- and noise-induced hearing loss...
March 7, 2018: Journal of Experimental Medicine
Haijuan Zhang, Baoxin Zhang, Cuixia Di, Mohammad Chand Ali, Jia Chen, Zhan Li, Jing Si, Hong Zhang, Hongdeng Qiu
As an important biomarker for the early stage of apoptosis, cytochrome c (Cyt c) has been recognized as a key component of the intrinsic apoptotic pathway. Fluorescence imaging tools enabling detection of Cyt c in apoptotic signaling have been rarely explored, though they are critical for cell biology and clinical theranostics. Here, we designed a novel label-free N-doped carbon dot (N-doped CD)-based nanosensor that enables fluorescence activation imaging of Cyt c release in cell apoptosis. The inner filter effect of Cyt c towards N-doped CDs enabled quantitative Cyt c measurement...
March 6, 2018: Nanoscale
Matthew R Broadus, Ethan Lee
Most drug screening methods use purified proteins, cultured cells, and/or small model organisms such as Xenopus , zebrafish, flies, or nematodes. These systems have proven successes in drug discovery, but they also have weaknesses. Although purified cellular components allow for identification of compounds with activity against specific targets, such systems lack the complex biological interactions present in cellular and organismal screens. In vivo systems overcome these weaknesses, but the lack of cellular permeability, efflux by cellular pumps, and/or toxicity can be major limitations...
February 23, 2018: Cold Spring Harbor Protocols
Katharine A Horzmann, Jennifer L Freeman
The laboratory zebrafish (Danio rerio) is now an accepted model in toxicologic research. The zebrafish model fills a niche between in vitro models and mammalian biomedical models. The developmental characteristics of the small fish are strategically being used by scientists to study topics ranging from high-throughput toxicity screens to toxicity in multi- and transgenerational studies. High-throughput technology has increased the utility of zebrafish embryonic toxicity assays in screening of chemicals and drugs for toxicity or effect...
February 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Aniket V Gore, Laura M Pillay, Marina Venero Galanternik, Brant M Weinstein
Hematopoiesis is a complex process with a variety of different signaling pathways influencing every step of blood cell formation from the earliest precursors to final differentiated blood cell types. Formation of blood cells is crucial for survival. Blood cells carry oxygen, promote organ development and protect organs in different pathological conditions. Hematopoietic stem and progenitor cells (HSPCs) are responsible for generating all adult differentiated blood cells. Defects in HSPCs or their downstream lineages can lead to anemia and other hematological disorders including leukemia...
February 13, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
Kingsley Ibhazehiebo, Cezar Gavrilovici, Cristiane L de la Hoz, Shun-Chieh Ma, Renata Rehak, Gaurav Kaushik, Paola L Meza Santoscoy, Lucas Scott, Nandan Nath, Do-Young Kim, Jong M Rho, Deborah M Kurrasch
Despite the development of newer anti-seizure medications over the past 50 years, 30-40% of patients with epilepsy remain refractory to treatment. One explanation for this lack of progress is that the current screening process is largely biased towards transmembrane channels and receptors, and ignores intracellular proteins and enzymes that might serve as efficacious molecular targets. Here, we report the development of a novel drug screening platform that harnesses the power of zebrafish genetics and combines it with in vivo bioenergetics screening assays to uncover therapeutic agents that improve mitochondrial health in diseased animals...
January 24, 2018: Brain: a Journal of Neurology
M Ender Avci, Ayse Gokce Keskus, Seniye Targen, M Efe Isilak, Mehmet Ozturk, Rengul Cetin Atalay, Michelle M Adams, Ozlen Konu
Acetylcholinesterase (AChE), an enzyme responsible for degradation of acetylcholine, has been identified as a prognostic marker in liver cancer. Although in vivo Ache tumorigenicity assays in mouse are present, no established liver cancer xenograft model in zebrafish using an ache mutant background exists. Herein, we developed an embryonic zebrafish xenograft model using epithelial (Hep3B) and mesenchymal (SKHep1) liver cancer cell lines in wild-type and ache sb55 sibling mutant larvae after characterization of cholinesterase expression and activity in cell lines and zebrafish larvae...
January 25, 2018: Scientific Reports
Lucas Moritz Wiggenhauser, Katharina Kohl, Nadine Dietrich, Hans-Peter Hammes, Jens Kroll
Diabetic retinopathy is the leading cause of blindness among middle-aged adults. The rising prevalence of diabetes worldwide will make the prevention of diabetic microvascular complications one of the key research fields of the next decades. Specialized, targeted therapy and novel therapeutic drugs are needed to manage the increasing number of patients at risk of vision-loss. The zebrafish is an established animal model for developmental research questions with increasing relevance for modeling metabolic multifactorial disease processes...
December 26, 2017: Journal of Visualized Experiments: JoVE
Hifsa Zahid, Benjamin Tsang, Hira Ahmed, Richard Chi Yeung Lee, Steven Tran, Robert Gerlai
The growing popularity of zebrafish in psychopharmacology and behavioral brain research is partly due to the practicality and simplicity of drug administration in this species. Several drugs may be administered to zebrafish by immersing the fish in the drug solution. Furthermore, numerous drugs developed for mammals, including humans, have been found to show a similar effect profile in the zebrafish. Thus, the zebrafish has been suggested as a potentially useful animal screening tool. Despite decades of drug development, anxiety still represents a major unmet medical need, and the search for anxiolytic compounds is continuing...
January 19, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Eduard Dumitrescu, Kenneth Wallace, Silvana Andreescu
Nitric oxide (NO) is an important signaling molecule that has been implicated in a variety of physiological and pathophysiological processes in living organisms. NO plays an important role in embryonic development in vertebrates and has been reported to influence early organ development and plasticity. Quantifying NO in single embryos and their developing organs is challenging because of the small size of the embryos, the low dynamically changing concentration and the short life-time of NO. Here, we measured the distribution of NO in the intestine of live zebrafish (Danio rerio) embryos in physiological conditions and under the influence of therapeutic agents...
January 16, 2018: Nitric Oxide: Biology and Chemistry
Peter M Eimon, Mostafa Ghannad-Rezaie, Gianluca De Rienzo, Amin Allalou, Yuelong Wu, Mu Gao, Ambrish Roy, Jeffrey Skolnick, Mehmet Fatih Yanik
Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson's disease...
January 15, 2018: Nature Communications
Kai-Di Hsu, Yu-Hin Chan, Hong-Jhang Chen, Shi-Ping Lin, Kuan-Chen Cheng
Tyrosinase-based TLC (thin layer chromatography) was developed for screening of anti-melanogenic drugs. In particular, this technique enables researchers to identify melanogenic inhibitor(s) in tested mixtures with the naked eye. In comparison with traditional colorimetric screening assays for tyrosinase inhibitor(s), not only is tyrosinase-based TLC a more cost-effective option (nearly one-tenth the enzyme cost of colorimetric methods) but also is a more sensitive detection approach for kojic acid (KA), a standard anti-melanogenic drug...
January 10, 2018: Scientific Reports
Wenjuan Zhang, Jingjin Xu, Juhui Qiu, Cencan Xing, Xiumin Li, Bo Leng, Yi Su, Jinmei Lin, Jiaofen Lin, Xuqiao Mei, Yiqun Huang, Yutian Pan, Yu Xue
Osteoporosis is a global public health concern and, it can result from numerous pathogenic mechanisms, many of which are closely related with age, nutritional disorders, endocrine imbalance, or adverse drug side effects presented by glucocorticoids, heparin, and anti-epileptics. Given its wide range etiologies, it is crucial to establish an animal model of osteoporosis for use in screening potential drugs quickly and effectively. Previous research has reported that an accumulation of elevated iron in the body is an independent risk factor for osteoporosis...
February 5, 2018: Biochemical and Biophysical Research Communications
Lifeng Liu, Guang Yang, Shoupeng Liu, Linbo Wang, Xibin Yang, Huiming Qu, Xiaofen Liu, Le Cao, Weijun Pan, Hui Li
High-throughput imaging and screening is essential for biomedical research and drug discovery using miniature model organisms such as zebrafish. This study introduces a high-speed imaging system which illuminates zebrafish embryos flowing through a capillary tube with a sheet of light and captures them using a linear charge-coupled device (CCD). This system can image dozens of zebrafish embryos per second. An image algorithm was developed to recognize each embryo and to perform automatic analysis. We distinguished dead and living embryos according to the gray level distribution and conducted statistics of morphological characteristics of embryos at different growing stages...
December 1, 2017: Biomedical Optics Express
Lilian B Romero-Sánchez, Manuel Marí-Beffa, Paloma Carrillo, Miguel Ángel Medina, Aránzazu Díaz-Cuenca
The osteogenic and angiogenic responses of organisms to the ionic products of degradation of bioactive glasses (BGs) are being intensively investigated. The promotion of angiogenesis by copper (Cu) has been known for more than three decades. This element can be incorporated to delivery carriers, such as BGs, and the materials used in biological assays. In this work, Cu-containing mesoporous bioactive glass (MBG) in the SiO2-CaO-P2O5 compositional system was prepared incorporating 5% mol Cu (MBG-5Cu) by replacement of the corresponding amount of Ca...
December 27, 2017: Acta Biomaterialia
A C Berrun, D L Stachura
Hematopoiesis is an essential cellular process in which hematopoietic stem and progenitor cells (HSPCs) differentiate into the multitude of different cell lineages that comprise mature blood. Isolation and identification of these HSPCs is difficult because they are defined ex post facto; they can only be defined after their differentiation into specific cell lineages. Over the past few decades, the zebrafish (Danio rerio) has become a model organism to study hematopoiesis. Zebrafish embryos develop ex utero, and by 48 h post-fertilization (hpf) have generated definitive HSPCs...
November 30, 2017: Journal of Visualized Experiments: JoVE
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