Adverse outcome pathways during zebrafish embryogenesis: A case study with paraoxon

Yozzo, Krystle L.; McGee, Sean P.; Volz, David C.

doi:10.1016/j.aquatox.2012.09.008

Cited by 41 publications

(28 citation statements)

References 36 publications

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“…As image acquisition within our assay occurred during the peak frequency of spontaneous tail contractions (25–26 hpf when reared at 28°C) (Yozzo et al, 2013), LOPAC 1280 compounds that interfere with electrical coupling and/or chemically-mediated neurotransmission may have the potential to adversely affect late spontaneous activity following a 5–25 hpf exposure. Based on results from both screens, spontaneous activity was similarly impacted by LOPAC 1280 compounds targeting neurotransmission- and non-neurotransmission-related processes, where the magnitude of effect following a 10-μM exposure was, in a number of cases, equivalent for both groups of compounds.…”

Section: Discussionmentioning

confidence: 99%

Behavioral screening of the LOPAC1280 library in zebrafish embryos

Vliet

Volz

2017

Toxicology and Applied Pharmacology

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Spontaneous activity represents an early, primitive form of motor activity within zebrafish embryos, providing a potential readout for identification of neuroactive compounds. However, despite use as an endpoint in chemical screens around the world, the predictive power and limitations of assays relying on spontaneous activity remain unclear. Using an improved high-content screening assay that increased throughput from 384 to 3,072 wells per week, we screened a well-characterized library of 1,280 pharmacologically active compounds (LOPAC1280) – 612 of which target neurotransmission – to identify which targets are detected using spontaneous activity as a readout. Results from this screen revealed that (1) 8% of the LOPAC1280 library was biologically active; (2) spontaneous activity was affected by compounds spanning a broad array of targets; (3) only 4% of compounds targeting neurotransmission impacted spontaneous activity; and (4) hypoactivity was observed for 100% of hits detected, including those that exhibit opposing mechanisms of action for the same target. Therefore, while this assay was able to rapidly identify potent neuroactive chemicals, these data suggest that spontaneous activity may lack the ability to discriminate modes of action for compounds interfering with neurotransmission, an issue that may be due to systemic uptake following waterborne exposure, persistent control variation, and/or interference with non-neurotransmission-related mechanisms.

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Section: Discussionmentioning

confidence: 99%

Behavioral screening of the LOPAC1280 library in zebrafish embryos

Vliet

Volz

2017

Toxicology and Applied Pharmacology

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“…There are contradicting results from a number of publications on this topic. In a study with paraoxon, significant AChE inhibition (36% of control) was achieved, yet there was no effect on the development of secondary motor neurons . In another study, however, significant AChE inhibition (<10% of control) produced by similar concentrations of chlorpyrifos oxon significantly hindered axonal growth of sensory, primary, and secondary neurons .…”

Section: Op Pesticide–induced Developmental Toxicity and Behavioral Dmentioning

confidence: 95%

“…A number of publications have described the developmental consequences of exposure to subacute concentrations of AChE‐inhibiting OP pesticides in embryonic, larval, and adult zebrafish, such as chlorpyrifos/chlorpyrifos oxon, azinphos‐methyl, parathion/paraoxon, malathion, dichlorvos, and diazinon . The major observations from a number of these studies are summarized in Table .…”

Section: Op Pesticide–induced Developmental Toxicity and Behavioral Dmentioning

confidence: 99%

Zebrafish as a model for acetylcholinesterase‐inhibiting organophosphorus agent exposure and oxime reactivation

Koenig

Dao

Kan

et al. 2016

Annals of the New York Academy of Sciences

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The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE), including pesticides and chemical warfare nerve agents (CWNAs), rely solely on in vitro cell assays and in vivo rodent models. The zebrafish (Danio rerio) is a popular, well-established vertebrate model in biomedical research that offers high-throughput capabilities and genetic manipulation not readily available with rodents. A number of research studies have investigated the effects of subacute developmental exposure to OP pesticides in zebrafish, observing detrimental effects on gross morphology, neuronal development, and behavior. Few studies, however, have utilized this model to evaluate treatments, such as oxime reactivators, anticholinergics, or anticonvulsants, following acute exposure. Preliminary work has investigated the effects of CWNA exposure. The results clearly demonstrated relative toxicity and oxime efficacy similar to that reported for the rodent model. This review surveys the current literature utilizing zebrafish as a model for OP exposure and highlights its potential use as a high-throughput system for evaluating AChE reactivator antidotal treatments to acute pesticide and CWNA exposure.

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“…For example, inhibition of acetylcholinesterase is one of the most studied and best understood neurotoxic mechanisms in zebrafish larvae. Besides data on behavioural effects , data is available on axonal outgrowth of different sensory and motor neurons (Jacobson et al 2010;Yang et al 2011), AChE activity (Yozzo et al 2013), neurogenesis in AChE knock-out mutants (Downes and Granato 2004) and gene expression changes (Klüver et al 2011). Yozzo et al (2013) even defined an 'adverse outcome pathway' for acetylcholinesterase inhibition.…”

Section: Mechanistic Characterization Of Behavioural Responsesmentioning

confidence: 99%

Comparability of behavioural assays using zebrafish larvae to assess neurotoxicity

Legradi

Abdellaoui

Pomeren

et al. 2014

Environ Sci Pollut Res

104

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Testing of compounds for neurotoxicity has become increasingly important in recent years. It has been shown that neurological disorders like autism may be related to chemical exposures, which may play a crucial role in the progression of these diseases. Special attention has been be given to the substances causing developmental neurotoxicity as the developing nervous system is more vulnerable to impacts by chemicals than the adult nervous system. The zebrafish (Danio rerio) is a well-established model species in developmental biology and an emerging model in behavioural and neurological studies. Zebrafish larvae display numerous behavioural patterns highly similar to rodents and humans. Their physical characteristics make them well suited for automated high-throughput screening. In the last years, the number of behavioural studies conducted with zebrafish larvae has increased notably. The goal of this review is to provide an overview of behavioural assays commonly used to test substances for developmental neurotoxicity. Literature from 1995 to 2014 was reviewed and focussed on assays performed with zebrafish larvae younger than 7 days post fertilization (dpf). The behavioural tests were scrutinized, and parameters describing the different experimental setups were defined. In the next step, we investigated if differences in the experimental parameters alter the outcome of the test. In order to test the comparability of behavioural assays, we analysed several studies using ethanol, valproate and pentylenetetrazole as model substances. Based on our findings, we provide recommendations which could help improve future behavioural studies performed with zebrafish larvae.

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Adverse outcome pathways during zebrafish embryogenesis: A case study with paraoxon

Cited by 41 publications

References 36 publications

Behavioral screening of the LOPAC1280 library in zebrafish embryos

Behavioral screening of the LOPAC1280 library in zebrafish embryos

Zebrafish as a model for acetylcholinesterase‐inhibiting organophosphorus agent exposure and oxime reactivation

Comparability of behavioural assays using zebrafish larvae to assess neurotoxicity

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