We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multidimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors.
Maxinne Watchon, Kristy C. Yuan, Nick Mackovski, Adam J. Svahn, Nicholas J. Cole, Claire Goldsbury, Silke Rinkwitz, Thomas S. Becker, Garth A. Nicholson and Angela S. Laird
OptoGluNAM4.1, a Photoswitchable Allosteric Antagonist for Real-Time Control of mGlu4 Receptor Activity.
Jingjing Han, Cheng Ji, Yichen Guo, Rui Yan, Ting Hong, Yuanyan Dou, Yan An, Shasha Tao, Fenju Qin, Jihua Nie, Chen Ji, Han Wang, Jian Tong, Wei Xiao & Jie Zhang
Keywords Buprenorphine; Cyclooxygenase-2; Nociception; Pain; Zebrafish larvae
Highlights • Adult rest mutants engage in erratic swimming and display atypical spatial preferences. • rest mutant larvae are hypoactive when compared to sibling controls. • Adult rest mutant males but not females show diminished reproductive success.
Highlights • The zebrafish embryotoxicity test (ZET) was applied using integrated multiple endpoints. • Morphology, motor activity, histopathology, kinetics and gene expression were studied. • A series of anti-epileptic drugs showed specific sensitivity for each endpoint. • This test strategy may contribute to elucidate the mode of action for developmental toxicity in ZET. • This test strategy may contribute to better define the applicability domain of the ZET.
Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) ...
HIGHLIGHTS - The zebrafish embryotoxicity test (ZET) was applied using integrated multiple endpoints - Morphology, motor activity, histopathology, kinetics and gene expression were studied - A series of anti-epileptic drugs showed specific sensitivity for each endpoint - This test strategy may contribute to elucidate the mode of action for developmental toxicity in ZET - This test strategy may contribute to better define the applicability domain of the ZET
As the population grows, so does the drive for urbanization. Urbanization and the resulting anthropogenic activities have an impact on the quality of nearby water resources. Puerto Rico’s population density is one of the highest in the world. We seek to develop a protocol to measure how Puerto Rico´s high level of urban development has impacted the behavior and nervous system function of river fauna. We have started by recording movement trajectory and velocity of freshwater prawn larvae during five consecutive periods of 10-minutes light/dark cycles, using ViewPoint´s Zebrabox.
Highlights • Both asic1 mRNA and protein expressions were detected in the adult zebrafish retina. • Acidosis-induced currents in the isolated retinal ganglion cells (RGCs) were recorded using whole cell patch clamping. • Blockade of ASICs channel significantly reduced the locomotion of larval zebrafish in response to light exposure.
Highlights • Zebrafish trpm7 mutant larvae exhibit dopamine-responsive behavioral deficits. • In such larvae, dopaminergic neurons express DAT but many lack expression of TH. • trpm7 mutant larvae are hyper-sensitive to a toxin of dopaminergic neurons, MPP+. • We show that SH-SY5Y cells, which are dopaminergic, depend on TRPM7 for survival. • How Trpm7 contributes to function and viability of dopaminergic neurons is unknown.
Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory.
The zebrafish-based assay is a widely used animal model system for cardiovascular research. In this study, we investigated the cardiac defects caused by terfenadine and tested the pharmacological response of digoxin to zebrafish with cardiac defects.
The underlying processes of nociception and pain are, despite the rodent models available, still not fully understood. One of the drawbacks of rodent model systems is the difficulty to screen compound libraries for their influence on nociception, thus slowing down the discovery of novel analgesics for clinical use.
In this study, we applied structure-based virtual screening techniques to identify natural product or natural product-like inhibitors of iNOS.
Ecotoxicology with the ZebraBox
The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy.
Eriocaulon buergerianum extract protects PC12 cells and neurons in zebrafish against 6-hydroxydopamine-induced damage
Toxicity assessment of zebraﬁsh following exposure to CdTe QDs
Genomic and functional conservation of sedative-hypnotic targets in the zebrafish
Interhemispheric asymmetry of olfactory input dependent neuronal specification in the adult brain
Normal and visually-impaired zebrafish larvae have differentiable light-induced locomotor response (LLR), which is composed of visual and non-visual components
Zebrafish care The Wild Indian Karyotype (WIK) strain of zebrafish was reared in community tanks on a 14-hour light, 10-hour dark cycle. Fish were fed twice a day, once with formulated feed (Dr. Bassleer Biofish Food) and once with Artemia larvae (cysts from Ocean Nutrition Europe). Eggs were collected 20 minutes after natural spawning and rinsed with system water to minimize infections. Embryos were raised at 28 ± 0.5°C in Danieau's medium. All animal experiments were approved by the Institutional Ethical Committee of the Katholieke Universiteit Leuven and executed in strict accordance with the European Council Directive (2010/63/EC).
The link between tobacco use and the development of serious diseases such as certain cancers, heart disease, respiratory diseases and stroke are well established . Despite this, tobacco use continues to be a growing global epidemic and remains the leading cause of preventable death worldwide . More than 37,000 Canadians have been estimated to die prematurely on an annual basis as a consequence of tobacco smoking  and costs to the health care system are estimated at over $4.3 billion annually . As such, tobacco use remains a public health concern in Canada.
Elmonem, M. A. et al. Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction. Sci. Rep. 7, 42583; doi: 10.1038/srep42583 (2017).
Measuring Larval Zebrafish Behavior: Locomotion, Thigmotaxis, and StartleMeasuring Larval Zebrafish Behavior: Locomotion, Thigmotaxis, and Startle
Extensive ethnopharmaceutical documentation is available on plants with demonstrated psychoactivity in humans (for review (Raetsch 2005)). Even though there is a huge need for new molecules in mental health, this reservoir of knowledge remains greatly untapped. One of the main reasons is probably the lack of a good in vivo system allowing testing of psychoactive efficacy of complex mixtures of unknown composition. Ethnobotanical reports on a specific plant often differ on plant species/subspecies/harvest but also on mode of preparation and administration which all generate a number of imponderable parameters. Therefore, it is necessary to establish a system which would be capable of circumventing those problems. Ideally, the proposed system has to be flexible and sensitive enough to allow rapid and systematic screening of a big number of complex mixtures like crude plants extracts. In such a system, first pass screening could be done with minimally processed extracts like preparations made from dried powdered parts of a plant of interest. Subsequently, gradually refined mixtures could be tested the same way to eventually isolate the active compound(s).
8–48 hpf is the sensitive exposure window for neurodevelopmental and behavioral toxicities of TBBPA. TBBPA induced apoptotic cell death and affected motor neuron and muscle fiber development. Zebrafish embryos rapidly absorbed and accumulated TBBPA, and eliminated it quickly. • TBBPA induced ugt genes expression, which increased T4 metabolism and subsequently induced neurobehavior defects.
Low dose TBBPA chronic exposure reduced zebrafish body weight and length. TBBPA exposure induced adult zebrafish hyperactivity with magnitude bigger in males than in females. Low dose TBBPA exposure induced male zebrafish heightened aggression using mirror attack test.
Highlights Custom-made economic imaging setup for distraction-free behavioural recording. ImageJ based algorithm for fast and automated tracking of Zebrafish without plugins. Mathematical workflow for extraction of behavioural endpoints. New representation for spatio-temporal nature of choice-based behaviours.
Zhang, C. et al. Hormetic effect of panaxatriol saponins confers neuroprotection in PC12 cells and zebrafish through PI3K/AKT/mTOR and AMPK/SIRT1/FOXO3 pathways. Sci. Rep. 7, 41082; doi: 10.1038/srep41082 (2017).
Best, C. et al. Maternal cortisol stimulates neurogenesis and affects larval behaviour in zebrafish. Sci. Rep. 7, 40905; doi: 10.1038/srep40905 (2017).
Zhang G, Truong L, Tanguay RL, Reif DM (2017) A New Statistical Approach to Characterize Chemical-Elicited Behavioral Effects in High-Throughput Studies Using Zebrafish. PLoS ONE 12(1): e0169408. doi:10.1371/journal.pone.0169408
VU University in Amsterdam uses the Zebrabox technology to investigate the effect of micro-pollutants.
Drug Screening to Treat Early-Onset Eye Diseases: Can Zebrafish Expedite the Discovery?
Hundreds of top universities and companies using the ZebraBox.
With recent advances in behavior tracking technology, we were able to develop a new behavioral analysis multi-cell exposure system named “Multi-DaphTrack” with a high-throughput testing capacity for assessing the behavioral response of Daphnia magna
Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish