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Zebrafish drug screen

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https://www.readbyqxmd.com/read/28438663/acute-effects-of-amitriptyline-on-adult-zebrafish-potential-relevance-to-antidepressant-drug-screening-and-modeling-human-toxidromes
#1
Konstantin A Demin, Tatiana O Kolesnikova, Sergey L Khatsko, Darya M Meshalkina, Evgeniya V Efimova, Yuri Yu Morzherin, Allan V Kalueff
The need to develop novel antidepressants is an emerging problem in biomedicine. An aquatic vertebrate species, the zebrafish (Danio rerio) may serve as a useful in-vivo screen for CNS drugs, and displays high sensitivity to a wide range of antidepressants. Amitriptyline is a commonly used tricyclic antidepressant which acts primarily as a serotonin and noradrenaline reuptake inhibitor. Here, we characterize drug-induced behavioral and neurochemical responses in adult zebrafish following their acute exposure to amitriptyline...
April 21, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28431223/pink1-based-screen-shines-light-on-autophagy-enhancers-for-parkinson-s-disease
#2
Dominik Haddad, Ken Nakamura
In this issue of Cell Chemical Biology, Zhang et al. (2017) report a zebrafish model of Parkinson's disease (PD), incorporating the PD-protein PINK1 and rotenone, a toxin linked to PD. Using it as a drug-screening platform, they identify trifluoperazine and other piperazine phenothiazines as protective compounds that enhance autophagy independent of PINK1.
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28424313/reduction-in-activity-by-noxious-chemical-stimulation-is-ameliorated-by-immersion-in-analgesic-drugs-in-zebrafish
#3
Javier Lopez-Luna, Qussay Al-Jubouri, Waleed Al-Nuaimy, Lynne U Sneddon
Research has recently demonstrated that larval zebrafish show similar molecular responses to nociception to those of adults. Our study explored whether unprotected larval zebrafish exhibited altered behaviour after exposure to noxious chemicals and screened a range of analgesic drugs to determine their efficacy to reduce these responses. This approach aimed to validate larval zebrafish as a reliable replacement for adults as well as providing a high-throughput means of analysing behavioural responses. Zebrafish at 5 days post-fertilization were exposed to known noxious stimuli: acetic acid (0...
April 15, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28423345/homocysteine-induced-peripheral-microcirculation-dysfunction-in-zebrafish-and-its-attenuation-by-l-arginine
#4
Sang Joon Lee, Sung Ho Park, Jinhyuk Fred Chung, Woorak Choi, Hyung Kyu Huh
Elevated blood homocysteine (Hcy) level is frequently observed in aged individuals and those with age-related vascular diseases. However, its effect on peripheral microcirculation is still not fully understood. Using in vivo zebrafish model, the degree of Hcy-induced peripheral microcirculation dysfunction is assessed in this study with a proposed dimensionless velocity parameter V¯CV/V¯PCV, where V¯CV and V¯PCV represent the peripheral microcirculation perfusion and the systemic perfusion levels, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422076/zeglobaltox-an-innovative-approach-to-address-organ-drug-toxicity-using-zebrafish
#5
Carles Cornet, Simone Calzolari, Rafael Miñana-Prieto, Sylvia Dyballa, Els van Doornmalen, Helma Rutjes, Thierry Savy, Davide D'Amico, Javier Terriente
Toxicity is one of the major attrition causes during the drug development process. In that line, cardio-, neuro-, and hepatotoxicities are among the main reasons behind the retirement of drugs in clinical phases and post market withdrawal. Zebrafish exploitation in high-throughput drug screening is becoming an important tool to assess the toxicity and efficacy of novel drugs. This animal model has, from early developmental stages, fully functional organs from a physiological point of view. Thus, drug-induced organ-toxicity can be detected in larval stages, allowing a high predictive power on possible human drug-induced liabilities...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28409342/zebrafish-as-a-model-of-kidney-disease
#6
Elvin E Morales, Rebecca A Wingert
Animal models have been an invaluable means to advance biomedical research as they provide experimental avenues for cellular and molecular investigations of disease pathology. The zebrafish (Danio rerio) is a good alternative to mammalian models that can be used to apply powerful genetic experimental methods normally used in invertebrates to answer questions about vertebrate development and disease. In the case of the kidney, the zebrafish has proven itself to be an applicable and versatile experimental system, mainly due to the simplicity of its pronephros, which contains two nephrons that possess conserved structural and physiological aspects with mammalian nephrons...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28408289/dopaminergic-control-of-anxiety-in-young-and-aged-zebrafish
#7
Victoria Kacprzak, Neil A Patel, Elizabeth Riley, Lili Yu, Jing-Ruey J Yeh, Irina V Zhdanova
Changes in the expression of the dopamine transporter (DAT), or the sensitivity of dopamine receptors, are associated with aging and substance abuse and may underlie some of the symptoms common to both conditions. In this study, we explored the role of the dopaminergic system in the anxiogenic effects of aging and acute cocaine exposure by comparing the behavioral phenotypes of wildtype (WT) and DAT knockout zebrafish (DAT-KO) of different ages. To determine the involvement of specific dopamine receptors in anxiety states, antagonists to D1 (SCH23390) and D2/D3 (sulpiride) were employed...
April 10, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28385158/a-multi-animal-tracker-for-studying-complex-behaviors
#8
Eyal Itskovits, Amir Levine, Ehud Cohen, Alon Zaslaver
BACKGROUND: Animals exhibit astonishingly complex behaviors. Studying the subtle features of these behaviors requires quantitative, high-throughput, and accurate systems that can cope with the often rich perplexing data. RESULTS: Here, we present a Multi-Animal Tracker (MAT) that provides a user-friendly, end-to-end solution for imaging, tracking, and analyzing complex behaviors of multiple animals simultaneously. At the core of the tracker is a machine learning algorithm that provides immense flexibility to image various animals (e...
April 6, 2017: BMC Biology
https://www.readbyqxmd.com/read/28378824/chemical-inhibition-reveals-differential-requirements-of-signaling-pathways-in-kras-v12-and-myc-induced-liver-tumors-in-transgenic-zebrafish
#9
Chuan Yan, Qiqi Yang, Xiaojing Huo, Hankun Li, Li Zhou, Zhiyuan Gong
Previously we have generated inducible liver tumor models by transgenic expression of an oncogene and robust tumorigenesis can be rapidly induced by activation of the oncogene in both juvenile and adult fish. In the present study, we aimed at chemical intervention of tumorigenesis for understanding molecular pathways of tumorigenesis and for potential development of a chemical screening tool for anti-cancer drug discovery. Thus, we evaluated the roles of several major signaling pathways in kras(V12)- or Myc-induced liver tumors by using several small molecule inhibitors: SU5402 and SU6668 for VEGF/FGF signaling; IWR1 and cardionogen 1 for Wnt signaling; and cyclopamine and Gant61 for Hedgehog signaling...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28366621/rescue-of-pink1-deficiency-by-stress-dependent-activation-of-autophagy
#10
Yuxi Zhang, David T Nguyen, Ellen M Olzomer, Gin P Poon, Nicholas J Cole, Anita Puvanendran, Brigitte R Phillips, Daniel Hesselson
Stimulating autophagy is a promising therapeutic strategy for slowing the progression of neurodegenerative disease. Neurons are insensitive to current approaches based on mTOR inhibition for activating autophagy, and instead may rely on the Parkinson's disease-associated proteins PINK1 and PARKIN to activate the autophagy-lysosomal pathway in response to mitochondrial damage. We developed a multifactorial zebrafish drug-screening platform combining Pink1 deficiency with an environmental toxin to compromise mitochondrial function and trigger dopaminergic neuron loss...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28359882/re-examining-the-factors-affecting-choice-in-the-light-dark-preference-test-in-zebrafish
#11
Amanda Facciol, Steven Tran, Robert Gerlai
The light-dark preference test has been extensively used to screen anxiolytic drugs and investigate mechanisms of anxiety with rodents. Recently, this task has been adapted to zebrafish, but a number of inconsistent findings have emerged. For example, some found zebrafish to avoid and others to prefer dark. Given the translational relevance of the zebrafish, its utility in high throughput drug screens, and that anxiety still represents a large unmet medical need, there is an urgent need to resolve these inconsistencies...
March 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28350247/the-transgenic-zebrafish-display-fluorescence-reflecting-the-expressional-dynamics-of-dihydrofolate-reductase
#12
Wen-Ni Chang, Wan-Yu Chi, Tseng-Ting Kao, Jen-Ning Tsai, Wangta Liu, Shih-Shin Liang, Chien-Chih Chiu, Bing-Hung Chen, Tzu-Fun Fu
Dihydrofolate reductase (DHFR) reduces folic acid and recycles dihydrofolate generated during dTMP biosynthesis to tetrahydrofolate. DHFR is upregulated in rapidly proliferating cells and hence a favored target of antifolate drug against cancers, autoimmune diseases, and microbial infections. However, increased expression of dhfr contributed to the often emerging drug resistance and impeded the therapeutic efficacy of antifolate drugs. Therefore, comprehensive knowledge on the expressional control of dhfr becomes crucial...
March 28, 2017: Zebrafish
https://www.readbyqxmd.com/read/28349300/behavioral-methods-for-the-functional-assessment-of-hair-cells-in-zebrafish
#13
REVIEW
Qin Yang, Peng Sun, Shi Chen, Hongzhe Li, Fangyi Chen
Zebrafish is an emerging animal model for studies on auditory system. This model presents high comparability with humans, good accessibility to the hearing organ, and high throughput capacity. To better utilize this animal model, methodologies need to be used to quantify the hearing function of the zebrafish. Zebrafish displays a series of innate and robust behavior related to its auditory function. Here, we reviewed the advantage of using zebrafish in auditory research and then introduced three behavioral tests, as follows: the startle response, the vestibular-ocular reflex, and rheotaxis...
March 27, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28348206/high-throughput-identification-of-small-molecules-that-affect-human-embryonic-vascular-development
#14
Helena Vazão, Susana Rosa, Tânia Barata, Ricardo Costa, Patrícia R Pitrez, Inês Honório, Margreet R de Vries, Dimitri Papatsenko, Rui Benedito, Daniel Saris, Ali Khademhosseini, Paul H A Quax, Carlos F Pereira, Nadia Mercader, Hugo Fernandes, Lino Ferreira
Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and potential adverse consequences in humans. To develop a screening platform for molecules that affect human embryonic development based on endothelial cells (ECs) derived from human pluripotent stem cells, we differentiated human pluripotent stem cells into embryonic ECs and induced their maturation under arterial flow conditions...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28335860/-muscling-throughout-life-integrating-studies-of-muscle-development-homeostasis-and-disease-in-zebrafish
#15
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
#16
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...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28288793/a-novel-zebrafish-based-model-of-nociception
#17
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
#18
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
#19
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
#20
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
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