Use of Zebrafish in Drug Discovery Toxicology

Chemical Research in Toxicology, Journal Year: 2019, Volume and Issue: 33(1), P. 95 - 118

Published: Oct. 18, 2019

Unpredicted human safety events in clinical trials for new drugs are costly terms of health and money. The drug discovery industry attempts to minimize those with diligent preclinical testing. Current standard practices good at preventing toxic compounds from being tested the clinic; however, false negative toxicity results still a reality. Continual improvement must be pursued realm. Higher-quality therapies can brought forward more information about potential toxicities associated mechanisms. zebrafish model is bridge between vitro assays mammalian vivo studies. This powerful its breadth application tractability research. In past two decades, our understanding disease biology has grown significantly owing thousands studies on this tiny vertebrate. Review summarizes challenges strengths model, discusses 3Rs value that it deliver, highlights translatable untranslatable biology, brings together reports recent focusing toxicology.

Language: Английский

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A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters

Nature Chemical Biology, Journal Year: 2018, Volume and Issue: 14(4), P. 352 - 360

Published: Feb. 26, 2018

Language: Английский

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Zebrafish Larvae as a Behavioral Model in Neuropharmacology

Biomedicines, Journal Year: 2019, Volume and Issue: 7(1), P. 23 - 23

Published: March 26, 2019

Zebrafish larvae show a clear and distinct pattern of swimming in response to light dark conditions, following the development swim bladder at 4 days post fertilization. This behavior is increasingly employed screening neuroactive drugs. The recent emergence high-throughput techniques for automatic tracking zebrafish has further allowed an objective efficient way finding subtle behavioral changes that could go unnoticed during manual observations. review highlights use as model compounds. We describe, brief, repertoire larvae. Then, we focus on utilization light-dark locomotion test identifying

Language: Английский

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Molecular psychiatry of zebrafish

Molecular Psychiatry, Journal Year: 2014, Volume and Issue: 20(1), P. 2 - 17

Published: Oct. 28, 2014

Language: Английский

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The developing utility of zebrafish models of neurological and neuropsychiatric disorders: A critical review

Experimental Neurology, Journal Year: 2017, Volume and Issue: 299, P. 157 - 171

Published: Oct. 11, 2017

Language: Английский

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An ecotoxicological view on neurotoxicity assessment

Environmental Sciences Europe, Journal Year: 2018, Volume and Issue: 30(1)

Published: Dec. 1, 2018

The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans environment. Currently neurotoxicity assessment is mostly performed to predict prevent harm human populations. Despite all efforts invested last years developing novel vitro or silico test systems, vivo tests with rodents still only accepted Europe. an increasing number reports species showing altered behaviour, not required therefore performed. Considering environmental contaminants neurotoxic potential, eco-neurotoxicity should be also considered assessment. In order do so systems needed that can cope differences within ecosystems. field, online-biomonitoring using behavioural information could used detect effects effect-directed analyses applied identify causing effect. Additionally, toxic pressure calculations combination mixture modelling use chemical monitoring data adverse prioritize pollutants laboratory testing. Cheminformatics based on computational toxicological from studies help neurotoxicants. An array assays covering different modes action screen compounds neurotoxicity. selection guided by AOPs relevant eco-neurotoxicity. able perform eco-neurotoxicity, methods need focus most sensitive ecosystem. A battery trophic levels might best approach. To implement into European assessment, cheminformatics screening as first approach eco-neurotoxic pollutants. second step, small assess risks

Language: Английский

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Comparative Analyses of Zebrafish Anxiety-Like Behavior Using Conflict-Based Novelty Tests

Zebrafish, Journal Year: 2017, Volume and Issue: 14(3), P. 197 - 208

Published: May 1, 2017

Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized neuroscience research central nervous system (CNS) drug discovery. Representing the most commonly used models, novel tank test (NTT) focuses on diving response to potentially threatening stimuli, whereas light-dark (LDT) based fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate utility these two tests, combining meta-analyses published literature with comparative vivo behavioral whole-body endocrine (cortisol) testing. Overall, NTT LDT behaviors demonstrate a generally good cross-test correlation vivo, show that both tests have similar sensitivity anxiety-like states. Finally, evokes higher levels cortisol, likely representing more stressful procedure than LDT. Collectively, our study reappraises studying states zebrafish, emphasizes their developing neurobehavioral research. These findings can help optimize screening procedures by choosing appropriate models testing anxiolytic or anxiogenic drugs.

Language: Английский

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Gaining translational momentum: More zebrafish models for neuroscience research

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2014, Volume and Issue: 55, P. 1 - 6

Published: March 1, 2014

Language: Английский

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Effectiveness of zebrafish models in understanding human diseases—A review of models

Heliyon, Journal Year: 2023, Volume and Issue: 9(3), P. e14557 - e14557

Published: March 1, 2023

Understanding the detailed mechanism behind every human disease, disorder, defect, and deficiency is a daunting task concerning clinical diagnostic tools for patients. Hence, closely resembling living or simulated model of paramount interest development testing probable novel drug rectifying conditions pertaining to various ailments. The animal that can be easily genetically manipulated suit study therapeutic motive an indispensable asset within last few decades, zebrafish models have proven their effectiveness by becoming such potent disease with use being extended avenues research understand underlying mechanisms diseases. As are explored as animals in understanding molecular basis genetics many diseases owing 70% genetic homology between genes; new fascinating facts about surfaced, establishing it very powerful tool upcoming research. These prospective areas near future using model. In this review, against several osteoporosis, atrial fibrillation, Noonan syndrome, leukemia, autism spectrum disorders, etc. has been discussed.

Language: Английский

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Zebrafish models in neuropsychopharmacology and CNS drug discovery

British Journal of Pharmacology, Journal Year: 2017, Volume and Issue: 174(13), P. 1925 - 1944

Published: Feb. 20, 2017

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish ( Danio rerio ) is increasingly utilized as a powerful animal model in neuropharmacology research vivo drug screening. Collectively, this makes useful tool for discovery identification disordered pathways. Here, we discuss models selected human disorders drug‐induced phenotypes. As well covering broad range brain (from anxiety psychoses to neurodegeneration), also summarize recent developments genetics small molecule screening, which markedly enhance disease modelling novel targets.

Language: Английский

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