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Zebrafish drug screen

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https://www.readbyqxmd.com/read/28335860/-muscling-throughout-life-integrating-studies-of-muscle-development-homeostasis-and-disease-in-zebrafish
#1
Michelle F Goody, Erin V Carter, Elisabeth A Kilroy, Lisa Maves, Clarissa A Henry
The proper development and function of skeletal muscle is vital for health throughout the lifespan. Skeletal muscle function enables posture, breathing, and locomotion; and also impacts systemic processes-such as metabolism, thermoregulation, and immunity. Diseases of skeletal muscle (myopathies, muscular dystrophies) and even some neurological, age-related, and metabolic diseases compromise muscle function and negatively affect health span and quality of life. There have been numerous, recent examples of studies on skeletal muscle development with exciting, therapeutic implications for muscle diseases...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28320616/high-content-screen-using-zebrafish-danio-rerio-embryos-identifies-a-novel-kinase-activator-and-inhibitor
#2
Werner J Geldenhuys, Sadie A Bergeron, Jackie E Mullins, Rowaa Aljammal, Briah L Gaasch, Wei-Chi Chen, June Yun, Lori A Hazlehurst
In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10μM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord and muscle development in zebrafish embryos...
February 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28288793/a-novel-zebrafish-based-model-of-nociception
#3
J Christopher Taylor, L Savannah Dewberry, Stacie K Totsch, Lindsey R Yessick, Jennifer J DeBerry, Stephen A Watts, Robert E Sorge
Chronic pain affects the lives of millions yearly, but few new treatments are available. Due to decreasing budgets and increasing costs of preclinical research, alternatives are sought with high translatability and low cost. Here we demonstrate the utility of a zebrafish-based model of nociception to serve as a novel screening tool for analgesic drugs. Zebrafish swimming behavior was measured following administration of various algogens including histamine, cinnamaldehyde, mustard oil, acetic acid and complete Freund's adjuvant...
March 10, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28250994/evaluation-of-the-hair-cell-regeneration-in-zebrafish-larvae-by-measuring-and-quantifying-the-startle-responses
#4
Changquan Wang, Zhenmin Zhong, Peng Sun, Hanbing Zhong, Hongzhe Li, Fangyi Chen
The zebrafish has become an established model organism for the study of hearing and balance systems in the past two decades. The classical approach to examine hair cells is to use dye to conduct selective staining, which shows the number and morphology of hair cells but does not reveal their function. Startle response is a behavior closely related to the auditory function of hair cells; therefore it can be used to measure the function of hair cells. In this study, we developed a device to measure the startle response of zebrafish larvae...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28245372/-establishment-of-a-xenografted-acute-myeloid-leukemia-model-by-using-zebrafish
#5
Yong-Bin Ye, Ming-Wan Zhang, Da-Fa Qiu, Zi-Wen Guo, Hui-Qing He, Xiao-Jun Xu
Objectve: To investigate the feasibility of establishing xenografted leukemia model by zebrafish, so as to provide the more direct model in vitro and experimental evidence for study of acute myeloid leukemia and screening of the drugs for targeting therapy. METHODS: Acute myeloid leukemia cell line KG-1a was labeled with red fluorescent dye-MitoRed, then the labeled cells were injected into the yolk sac of zebrafish embryos. Morphological observation, cell count and histopathological detection were used to analyse the infiltration and metastasis of KG-1a cells in zebrafish...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28241031/a-novel-early-onset-phenotype-in-a-zebrafish-model-of-merosin-deficient-congenital-muscular-dystrophy
#6
Sarah J Smith, Jeffrey C Wang, Vandana A Gupta, James J Dowling
Merosin deficient congenital muscular dystrophy (MDC1A) is a severe neuromuscular disorder with onset in infancy that is associated with severe morbidities (particularly wheelchair dependence) and early mortality. It is caused by recessive mutations in the LAMA2 gene that encodes a subunit of the extracellular matrix protein laminin 211. At present, there are no treatments for this disabling disease. The zebrafish has emerged as a powerful model system for the identification of novel therapies. However, drug discovery in the zebrafish is largely dependent on the identification of phenotypes suitable for chemical screening...
2017: PloS One
https://www.readbyqxmd.com/read/28217866/zebrafish-models-in-neuropsychopharmacology-and-cns-drug-discovery
#7
REVIEW
Kanza M Khan, Adam D Collier, Darya A Meshalkina, Elana V Kysil, Sergey L Khatsko, Tatyana Kolesnikova, Yury Yu Morzherin, Jason E Warnick, Allan V Kalueff, David J Echevarria
Despite high prevalence of neuropsychiatric disorders, their etiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in-vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. Covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modeling and the discovery of novel drug targets...
February 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28208716/cell-imaging-counting-as-a-novel-ex-vivo-approach-for-investigating-drug-induced-hepatotoxicity-in-zebrafish-larvae
#8
Xuan-Bac Nguyen, Stanislav Kislyuk, Duc-Hung Pham, Angela Kecskés, Jan Maes, Deirdre Cabooter, Pieter Annaert, Peter De Witte, Annelii Ny
Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28181494/microenvironment-derived-factors-driving-metastatic-plasticity-in-melanoma
#9
Isabella S Kim, Silja Heilmann, Emily R Kansler, Yan Zhang, Milena Zimmer, Kajan Ratnakumar, Robert L Bowman, Theresa Simon-Vermot, Myles Fennell, Ralph Garippa, Liang Lu, William Lee, Travis Hollmann, Joao B Xavier, Richard M White
Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis. Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITF(LO) versus proliferative/MITF(HI) states. Since MITF also induces pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments that induce a MITF(HI)/differentiated/proliferative state. Zebrafish imaging demonstrates that after extravasation, melanoma cells become pigmented and enact a gene expression program of melanocyte differentiation...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28168859/zebrafish-screens-for-new-colitis-treatments-a-bottom-up-approach
#10
Jou A Lee, Stephen A Renshaw
Many factors interact in the development and progression of inflammatory bowel disease. This complexity demands a combination of methods to disentangle the pathology of this disease. As reported by Oehlers et al. in this issue, the zebrafish drug screen is one simple approach that could enable the elucidation of the pathways involved in IBD and ultimately the discovery of new therapeutics.
February 2017: FEBS Journal
https://www.readbyqxmd.com/read/28154320/screening-for-chemical-suppressors-of-the-wnt-%C3%AE-catenin-signaling-pathway
#11
Naoyuki Nishiya
 Aberrant activation of Wnt/β-catenin canonical signaling is observed in multiple malignant tumors, and is recognized as an attractive therapeutic target for molecular targeted drugs. This signaling pathway is also involved in maintaining pluripotency in adult stem cells. Therefore, lowering potential stem cell toxicity is a key factor for the development of a Wnt/β-catenin signaling inhibitor. Here, we show Wnt/β-catenin pathway inhibitors with low toxicity, identified through phenotype-based screening using zebrafish embryos...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28153846/miconazole-protects-blood-vessels-from-matrix-metalloproteinase-9-dependent-rupture-and-hemorrhage
#12
Ran Yang, Yunpei Zhang, Dandan Huang, Xiao Luo, Liangren Zhang, Xiaojun Zhu, Xiaolin Zhang, Zhenming Liu, Jingyan Han, Jing-Wei Xiong
Hemorrhagic stroke accounts for 10-15% of all strokes and is strongly associated with mortality and morbidity worldwide, but its prevention and therapeutic interventions remain a major challenge. Here, we report the identification of miconazole as a hemorrhagic suppressor by a small-molecule screen in zebrafish. We found that a hypomorphic mutant fn40a, one of known β-pix mutant alleles in zebrafish, had the major symptoms of brain hemorrhage, vessel rupture, and inflammation as those in hemorrhagic stroke patients...
February 2, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28137236/the-use-of-the-zebrafish-model-to-aid-in-drug-discovery-and-target-validation
#13
Prusothman Yoganantharjah, Yann Gibert
The zebrafish is fast becoming a leading and prominent model organism used by researchers for developmental biology, and research in modeling human diseases in zebrafish is being undertaken at a fast pace. Many therapeutic areas, including oncology and cardiovascular diseases to name a few all have zebrafish models based on known disease mechanisms that are translatable to modes of action in humans. Many novel assays have been and are continuing to be developed to study human disease in zebrafish. Prominent methods to identify novel drug targets within the organism include, chemical mutagenesis, insertional mutagenesis and high throughput small molecule screens...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28129855/a-zebrafish-xenograft-model-for-studying-human-cancer-stem-cells-in-distant-metastasis-and-therapy-response
#14
L Chen, A Groenewoud, C Tulotta, E Zoni, M Kruithof-de Julio, G van der Horst, G van der Pluijm, B Ewa Snaar-Jagalska
Lethal and incurable bone metastasis is one of the main causes of death in multiple types of cancer. A small subpopulation of cancer stem/progenitor-like cells (CSCs), also known as tumor-initiating cells from heterogenetic cancer is considered to mediate bone metastasis. Although over the past decades numerous studies have been performed in different types of cancer, it is still difficult to track small numbers of CSCs during the onset of metastasis. With use of noninvasive high-resolution imaging, transparent zebrafish embryos can be employed to dynamically visualize cancer progression and reciprocal interaction with stroma in a living organism...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28129853/analysis-of-myelinated-axon-formation-in-zebrafish
#15
M D'Rozario, K R Monk, S C Petersen
Myelin is a lipid-rich sheath formed by the spiral wrapping of specialized glial cells around axon segments. Myelinating glia allow for rapid transmission of nerve impulses and metabolic support of axons, and the absence of or disruption to myelin results in debilitating motor, cognitive, and emotional deficits in humans. Because myelin is a jawed vertebrate innovation, zebrafish are one of the simplest vertebrate model systems to study the genetics and development of myelinating glia. The morphogenetic cellular movements and genetic program that drive myelination are conserved between zebrafish and mammals, and myelin develops rapidly in zebrafish larvae, within 3-5days postfertilization...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28123103/embryonic-exposure-to-the-environmental-neurotoxin-bmaa-negatively-impacts-early-neuronal-development-and-progression-of-neurodegeneration-in-the-sod1-g93r-zebrafish-model-of-amyotrophic-lateral-sclerosis
#16
Samantha Powers, Samantha Kwok, Emily Lovejoy, Tom Lavin, Roger Sher
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive paralysis and death within 2-5 years after diagnosis. Sporadic cases (SALS) comprise ∼90% of cases with the remaining 10% familial (FALS) caused by mutations in ∼27 genes. The vast heterogeneity seen in age and location of disease onset, rate of progression, and duration of disease have been linked with genetic and environmental influences in both SALS and FALS cases. Increased ALS incidence clusters in Guam, southern France, and Maryland have been linked with exposure to Beta-methylamino-L-alanine (BMAA), a non-proteinogenic amino acid produced by cyanobacteria, dinoflaggelates, and diatoms...
January 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28121224/a-new-probe-to-measure-autophagic-flux-in-vitro-and-in-vivo
#17
Hideaki Morishita, Takeshi Kaizuka, Yutaro Hama, Noboru Mizushima
Macroautophagy is a catabolic process that delivers cytoplasmic components via the autophagosome to lysosomes for degradation. Measuring autophagic activity is critical to dissect molecular mechanisms and functions of autophagy but remains challenging due to the lack of a definitive method. We have recently developed a new fluorescent probe, GFP-LC3-RFP-LC3ΔG, to assess autophagic flux. Upon intracellular expression, the probe is cleaved by ATG4 family proteases into equimolar amounts of GFP-LC3 and RFP-LC3ΔG...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28118493/anticonvulsant-effect-of-sodium-cyclamate-and-propylparaben-on-pentylenetetrazol-induced-seizures-in-zebrafish
#18
Antonella Pisera-Fuster, Sofía Otero, Alan Talevi, Luis Bruno-Blanch, Ramón Bernabeu
Screening for novel anticonvulsant drugs requires appropriate animal seizure models. Zebrafish provide small, accessible, and cost-efficient preclinical models applicable to high-throughput small molecule screening. Based on previous results in rodents, we have here examined the effects of artificial sweetener sodium cyclamate and antimicrobial agent sodium propylparaben on a model of pentylenetetrazole (PTZ)-induced seizures in zebrafish. Sodium cyclamate reduced the bursts of hyperactivity, the spasms, increased the latency to spasms, and the latency to seizure, while propylparaben increased the latency to spasms...
April 2017: Synapse
https://www.readbyqxmd.com/read/28117738/in-vitro-biotransformation-of-two-human-cyp3a-probe-substrates-and-their-inhibition-during-early-zebrafish-development
#19
Evy Verbueken, Derek Alsop, Moayad A Saad, Casper Pype, Els M Van Peer, Christophe R Casteleyn, Chris J Van Ginneken, Joanna Wilson, Steven J Van Cruchten
At present, the zebrafish embryo is increasingly used as an alternative animal model to screen for developmental toxicity after exposure to xenobiotics. Since zebrafish embryos depend on their own drug-metabolizing capacity, knowledge of their intrinsic biotransformation is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this in vitro study was to assess the activity of cytochrome P450 (CYP)-a group of drug-metabolizing enzymes-in microsomes from whole zebrafish embryos (ZEM) of 5, 24, 48, 72, 96 and 120 h post-fertilization (hpf) by means of a mammalian CYP substrate, i...
January 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28104252/novel-zebrafish-eae-model-a-quick-in-vivo-screen-for-multiple-sclerosis
#20
Pushkar Kulkarni, Swapna Yellanki, Raghavender Medishetti, Dharmarajan Sriram, Uday Saxena, Perumal Yogeeswari
INTRODUCTION: Pre-clinical drug discovery for multiple sclerosis (MS) is a labor intensive activity to perform in rodent models. This is owing to the long duration of disease induction and observation of treatment effects in an experimental autoimmune encephalomyelitis (EAE) model. We propose a novel adult zebrafish based model which offers a quick and simple protocol that can used to screen candidates as a step between in vitro experiments and rodent studies. The experiments conducted for this manuscript were to standardize a suitable model of EAE in adult zebrafish and validate it using known modulators...
January 2017: Multiple Sclerosis and related Disorders
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