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Zebrafish drug screen

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https://www.readbyqxmd.com/read/29789451/zebrafish-models-of-rare-hereditary-pediatric-diseases
#1
REVIEW
Máté Varga, Dorottya Ralbovszki, Eszter Balogh, Renáta Hamar, Magdolna Keszthelyi, Kálmán Tory
Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even when the mapping results are unambiguous, the affected gene might be of unknown function. In these cases, understanding how a particular genotype can result in a phenotype also needs carefully designed experimental work...
May 22, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29761115/depdc5-knockdown-causes-mtor-dependent-motor-hyperactivity-in-zebrafish
#2
Hortense de Calbiac, Adriana Dabacan, Elise Marsan, Hervé Tostivint, Gabrielle Devienne, Saeko Ishida, Eric Leguern, Stéphanie Baulac, Raul C Muresan, Edor Kabashi, Sorana Ciura
Objective: DEPDC5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in a wide range of inherited forms of focal epilepsy, associated with malformation of cortical development in certain cases. Identification of frameshift, truncation, and deletion mutations implicates haploinsufficiency of DEPDC5 in the etiology of focal epilepsy. DEPDC5 is a component of the GATOR1 complex, acting as a negative regulator of mTOR signaling. Methods: Zebrafish represents a vertebrate model suitable for genetic analysis and drug screening in epilepsy-related disorders...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29755353/importance-of-toxicokinetics-to-assess-the-utility-of-zebrafish-larvae-as-model-for-psychoactive-drug-screening-using-meta-chlorophenylpiperazine-mcpp-as-example
#3
Krishna Tulasi Kirla, Ksenia J Groh, Michael Poetzsch, Rakesh Kumar Banote, Julita Stadnicka-Michalak, Rik I L Eggen, Kristin Schirmer, Thomas Kraemer
The number of new psychoactive substances (NPS) increases rapidly, harming society and fuelling the need for alternative testing strategies. These should allow the ever-increasing number of drugs to be tested more effectively for their toxicity and psychoactive effects. One proposed strategy is to complement rodent models with zebrafish ( Danio rerio ) larvae. Yet, our understanding of the toxicokinetics in this model, owing to the waterborne drug exposure and the distinct physiology of the fish, is incomplete...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29750281/an-orthotopic-glioblastoma-animal-model-suitable-for-high-throughput-screenings
#4
Linda Pudelko, Steven Edwards, Mirela Balan, Daniel Nyqvist, Jonathan Al-Saadi, Johannes Dittmer, Ingrid Almlöf, Thomas Helleday, Lars Bräutigam
Background: Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies and clinically relevant orthotopic zebrafish models have been developed...
May 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29747866/understanding-taurine-cns-activity-using-alternative-zebrafish-models
#5
Nathana J Mezzomo, Barbara D Fontana, Allan V Kalueff, Leonardo J G Barcellos, Denis B Rosemberg
Taurine is a highly abundant "amino acid" in the brain. Although the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action...
May 7, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29740748/the-effects-of-chronic-amitriptyline-on-zebrafish-behavior-and-monoamine-neurochemistry
#6
Darya A Meshalkina, Elana V Kysil, Kristina A Antonova, Konstantin A Demin, Tatiana O Kolesnikova, Sergey L Khatsko, Raul R Gainetdinov, Polina A Alekseeva, Allan V Kalueff
Amitriptyline is a commonly used tricyclic antidepressant (TCA) inhibiting serotonin and norepinephrine reuptake. The exact CNS action of TCAs remains poorly understood, necessitating new screening approaches and novel model organisms. Zebrafish (Danio rerio) are rapidly emerging as a promising tool for pharmacological research of antidepressants, including amitriptyline. Here, we examine the effects of chronic 2-week exposure to 10 and 50 μg/L amitriptyline on zebrafish behavior and monoamine neurotransmitters...
May 8, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29736716/modulation-of-threat-response-in-larval-zebrafish
#7
Andrew J Rennekamp
High-throughput, whole-organism phenotypic drug screening is made possible using live zebrafish larvae. Many human drugs have now been shown to affect zebrafish larvae in similar ways, through homologous molecular mechanisms. At this stage in life, zebrafish are small enough to fit in multi-well, microliter plates, yet developed enough to exhibit complex phenotypes, such as hunting behaviors and avoidance of predators. Importantly, zebrafish larvae can be easily dosed via automated pipetting of chemical compounds directly into their liquid medium, without injection...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29729327/fish-the-better-model-in-human-heart-research-zebrafish-heart-aggregates-as-a-3d-spontaneously-cardiomyogenic-in-vitro-model-system
#8
REVIEW
Patricia Hodgson, Jake Ireland, Bianka Grunow
The zebrafish (ZF) has become an essential model for biomedical, pharmacological and eco-toxicological heart research. Despite the anatomical differences between fish and human hearts, similarities in cellular structure and conservation of genes as well as pathways across vertebrates have led to an increase in the popularity of ZF as a model for human cardiac research. ZF research benefits from an entirely sequenced genome, which allows us to establish and study cardiovascular mutants to better understand cardiovascular diseases...
May 2, 2018: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/29718741/high-throughput-behavioral-assay-to-investigate-seizure-sensitivity-in-zebrafish-implicates-zfhx3-in-epilepsy
#9
Tyson D Fuller, Trudi A Westfall, Tirthasree Das, Deborah V Dawson, Diane C Slusarski
Epilepsy, which affects ∼1% of the population, is caused by abnormal synchronous neural activity in the central nervous system (CNS). While there is a significant genetic contribution to epilepsy, the underlying causes for the majority of genetic cases remain unknown. The NIH Undiagnosed Diseases Project (UDP) utilized exome sequencing to identify genetic variants in patients affected by various conditions with undefined etiology, including epilepsy. Confirming the functional relevance of the candidate genes identified by exome sequencing in a timely manner is crucial to translating exome data into clinically useful information...
May 2, 2018: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29689077/zebrafish-based-identification-of-the-antiseizure-nucleoside-inosine-from-the-marine-diatom-skeletonema-marinoi
#10
Théo Brillatz, Chiara Lauritano, Maxime Jacmin, Supitcha Khamma, Laurence Marcourt, Davide Righi, Giovanna Romano, Francesco Esposito, Adrianna Ianora, Emerson F Queiroz, Jean-Luc Wolfender, Alexander D Crawford
With the goal of identifying neuroactive secondary metabolites from microalgae, a microscale in vivo zebrafish bioassay for antiseizure activity was used to evaluate bioactivities of the diatom Skeletonema marinoi, which was recently revealed as being a promising source of drug-like small molecules. A freeze-dried culture of S. marinoi was extracted by solvents with increasing polarities (hexane, dichloromethane, methanol and water) and these extracts were screened for anticonvulsant activity using a larval zebrafish epilepsy model with seizures induced by the GABAA antagonist pentylenetetrazole...
2018: PloS One
https://www.readbyqxmd.com/read/29680360/forebrain-glutamate-uptake-and-behavioral-parameters-are-altered-in-adult-zebrafish-after-the-induction-of-status-epilepticus-by-kainic-acid
#11
Ben Hur Marins Mussulini, Adriana Fernanda Kuckartz Vizuete, Marcos Braga, Luana Moro, Suelen Baggio, Emerson Santos, Gabriela Lazzarotto, Kamila Cagliari Zenki, Letícia Pettenuzzo, João Batista Texeira Rocha, Diogo Losch de Oliveira, Maria Elisa Calcagnotto, José Angelo Silveira Zuanazzi, Javier Santos Burgos, Eduardo Pacheco Rico
The development of new antiepileptic drugs is a high-risk/high-cost research field, which is made even riskier if the behavioral epileptic seizure profile is the unique approach on which the development is based. In order to increase the effectiveness of the screening conducted in the zebrafish model of status epilepticus (SE), the evaluation of neurochemical markers of SE would be of great relevance. Epilepsy is associated with changes in the glutamatergic system, and glutamate uptake is one of the critical parameters of this process...
April 19, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29672015/zebrafish-based-discovery-of-antiseizure-compounds-from-the-red-sea-pseurotin-a-2-and-azaspirofuran-a
#12
Daniëlle Copmans, Mostafa Rateb, Jioji N Tabudravu, Mercedes Pérez-Bonilla, Nina Dirkx, Riccardo Vallorani, Caridad Diaz, José Pérez Del Palacio, Alan J Smith, Rainer Ebel, Fernando Reyes, Marcel Jaspars, Peter A M de Witte
In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model...
April 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29670865/opposite-effects-of-two-human-atg10-isoforms-on-replication-of-a-hcv-sub-genomic-replicon-are-mediated-via-regulating-autophagy-flux-in-zebrafish
#13
Yu-Chen Li, Miao-Qing Zhang, Jing-Pu Zhang
Autophagy is a host mechanism for cellular homeostatic control. Intracellular stresses are symptoms of, and responses to, dysregulation of the physiological environment of the cell. Alternative gene transcription splicing is a mechanism potentially used by a host to respond to physiological or pathological challenges. Here, we aimed to confirm opposite effects of two isoforms of the human autophagy-related protein ATG10 on an HCV subgenomic replicon in zebrafish. A liver-specific HCV subreplicon model was established and exhibited several changes in gene expression typically induced by HCV infection, including overexpression of several HCV-dependent genes ( argsyn, leugpcr, rasgbd , and scaf-2 ), as well as overexpression of several ER stress related genes ( atf4, chop, atf6 , and bip )...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29653073/a-zebrafish-heart-failure-model-for-assessing-therapeutic-agents
#14
Xiao-Yu Zhu, Si-Qi Wu, Sheng-Ya Guo, Hua Yang, Bo Xia, Ping Li, Chun-Qi Li
Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection...
March 20, 2018: Zebrafish
https://www.readbyqxmd.com/read/29626799/lipid-reducing-activity-and-toxicity-profiles-of-a-library-of-polyphenol-derivatives
#15
Ralph Urbatzka, Sara Freitas, Andreia Palmeira, Tiago Almeida, João Moreira, Carlos Azevedo, Carlos Afonso, Marta Correia-da-Silva, Emilia Sousa, Madalena Pinto, Vitor Vasconcelos
Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo...
March 23, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29619162/crispr-cas9-induced-shank3b-mutant-zebrafish-display-autism-like-behaviors
#16
Chun-Xue Liu, Chun-Yang Li, Chun-Chun Hu, Yi Wang, Jia Lin, Yong-Hui Jiang, Qiang Li, Xiu Xu
Background: Human genetic and genomic studies have supported a strong causal role of SHANK3 deficiency in autism spectrum disorder (ASD). However, the molecular mechanism underlying SHANK3 deficiency resulting in ASD is not fully understood. Recently, the zebrafish has become an attractive organism to model ASD because of its high efficiency of genetic manipulation and robust behavioral phenotypes. The orthologous gene to human SHANK3 is duplicated in the zebrafish genome and has two homologs, shank3a and shank3b ...
2018: Molecular Autism
https://www.readbyqxmd.com/read/29604314/zebrafish-models-relevant-to-studying-central-opioid-and-endocannabinoid-systems
#17
REVIEW
Konstantin A Demin, Darya A Meshalkina, Elana V Kysil, Kristina A Antonova, Andrey D Volgin, Oleg A Yakovlev, Polina A Alekseeva, Maria M Firuleva, Anton M Lakstygal, Murilo S de Abreu, Leonardo J G Barcellos, Wandong Bao, Ashton J Friend, Tamara G Amstislavskaya, Denis B Rosemberg, Pavel E Musienko, Cai Song, Allan V Kalueff
The endocannabinoid and opioid systems are two interplaying neurotransmitter systems that modulate drug abuse, anxiety, pain, cognition, neurogenesis and immune activity. Although they are involved in such critical functions, our understanding of endocannabinoid and opioid physiology remains limited, necessitating further studies, novel models and new model organisms. Zebrafish (Danio rerio) is rapidly emerging as one of the most effective translational models in neuroscience and biological psychiatry. Due to their high physiological and genetic homology to humans, zebrafish may be effectively used to study the endocannabinoid and opioid systems...
March 28, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29590635/identification-of-protective-postexposure-mycobacterial-vaccine-antigens-using-an-immunosuppression-based-reactivation-model-in-the-zebrafish
#18
Henna Myllymäki, Mirja Niskanen, Hanna Luukinen, Mataleena Parikka, Mika Rämet
Roughly one third of the human population carries a latent Mycobacterium tuberculosis infection, with a 5-10% lifetime risk of reactivation to active tuberculosis and further spreading the disease. The mechanisms leading to the reactivation of a latent Mycobacterium tuberculosis infection are insufficiently understood. Here, we used a natural fish pathogen, Mycobacterium marinum , to model the reactivation of a mycobacterial infection in the adult zebrafish ( Danio rerio ). A low-dose intraperitoneal injection (∼40 colony-forming units) led to a latent infection, with mycobacteria found in well-organized granulomas surrounded by a thick layer of fibrous tissue...
March 13, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29588029/zebrafish-a-pharmacogenetic-model-for-anesthesia
#19
Victoria Bedell, Elena Buglo, Daniel Marcato, Christian Pylatiuk, Ralf Mikut, Johannes Stegmaier, Will Scudder, Maxwell Wray, Stephan Züchner, Uwe Strähle, Ravindra Peravali, Julia E Dallman
General anesthetics are small molecules that interact with and effect the function of many different proteins to promote loss of consciousness, amnesia, and sometimes, analgesia. Owing to the complexity of this state transition and the transient nature of these drug/protein interactions, anesthetics can be difficult to study. The zebrafish is an emerging model for the discovery of both new genes required for the response to and side effects of anesthesia. Here we discuss the tools available to manipulate the zebrafish genome, including both genetic screens and genome engineering approaches...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29543903/an-automated-system-for-rapid-cellular-extraction-from-live-zebrafish-embryos-and-larvae-development-and-application-to-genotyping
#20
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
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