N-Acetylcysteine-Amide Protects Against Acute Acrylamide Neurotoxicity in Adult Zebrafish.

Acrylamide (ACR) is a potent neurotoxicant that disrupts cellular redox homeostasis by depleting reduced glutathione (GSH) and inducing oxidative stress. Despite its well-characterized mechanism, no effective treatments for ACR-induced neurotoxicity currently exist. This study evaluates the therapeutic efficacy of N-acetylcysteine-amide (AD4), a blood-brain barrier (BBB)-permeable derivative of N-acetylcysteine, in a novel severe acute ACR neurotoxicity model in adult zebrafish.

Polluted water from a storage dam (Villa Victoria, méxico) induces oxidative damage, AChE activity, embryotoxicity, and behavioral changes in Cyprinus carpio larvae.

The Villa Victoria dam is one of the most important storage reservoirs in Mexico since it distributes water to more than 20 million inhabitants in the Metropolitan Zone of Mexico City. In this dam, the common carp (Cyprinus carpio) is an important food resource for the inhabitants, so the aim of this work was to evaluate the oxidative damage (lipoperoxidation, oxidized proteins, antioxidant enzymes activity and gene expression), AChE, embryotoxicity and behavioral changes in C. carpio embryos and larvae exposed to water from Villa Victoria dam for 24, 48, 72 and 96 h.

Analyzing the Effects of Age, Time of Day, and Experiment on the Basal Locomotor Activity and Light-Off Visual Motor Response Assays in Zebrafish Larvae.

The recent availability of commercial platforms for behavioral analyses in zebrafish larvae based on video-tracking technologies has exponentially increased the number of studies analyzing different behaviors in this model organism to assess neurotoxicity. Among the most commonly used assays in zebrafish larvae are basal locomotor activity (BLA) and visual motor responses (VMRs). However, the effect of different intrinsic and extrinsic factors that can significantly alter the outcome of these assays is still not well understood.

Cardiac and neurobehavioral impairments in three phylogenetically distant aquatic model organisms exposed to environmentally relevant concentrations of boscalid.

Boscalid (2-Chloro-N-(4'-chlorobiphenyl-2-yl) nicotinamide), a pyridine carboxamide fungicide, is an inhibitor of the complex II of the respiration chain in fungal mitochondria. As boscalid is only moderately toxic for aquatic organisms (LC > 1-10 mg/L), current environmental levels of this compound in aquatic ecosystems, in the range of ng/L-μg/L, are considered safe for aquatic organisms. In this study, we have exposed zebrafish (Danio rerio), Japanese medaka (Oryzias latipes) and Daphnia magna to a range of concentrations of boscalid (1-1000 μg/L) for 24 h, and the effects on heart rate (HR), basal locomotor activity (BLA), visual motor response (VMR), startle response (SR), and habituation (HB) to a series of vibrational or light stimuli have been evaluated.

Short-term exposure to environmental levels of nicotine and cotinine impairs visual motor response in zebrafish larvae through a similar mode of action: Exploring the potential role of zebrafish α7 nAChR.

The current view is that environmental levels of nicotine and cotinine, commonly in the ng/L range, are safe for aquatic organisms. In this study, 7 days post-fertilization zebrafish embryos have been exposed for 24 h to a range of environmental concentrations of nicotine (2.0 ng/L-2.

Analysis of sleep/wake cycles in zebrafish larvae.

Zebrafish larvae are a model organism increasingly used in the study of the effect of neuroactive chemicals on vertebrate sleep/wake cycles. Sleep disturbances have a negative impact on mood, cognition and overall health. Here we present a protocol to assess over 24 h sleep/wake cycles in zebrafish larvae subjected to 12 h light/dark periods in 48-well plates, using video-tracking technologies.

Neurotoxicity Assessment in Adult Danio rerio using a Battery of Behavioral Tests in a Single Tank.

The presence of neuropathological effects proved to be, for many years, the main endpoint for assessing the neurotoxicity of a chemical substance. However, in the last 50 years, the effects of chemicals on the behavior of model species have been actively investigated. Progressively, behavioral endpoints were incorporated into neurotoxicological screening protocols, and these functional outcomes are now routinely used to identify and determine the potential neurotoxicity of chemicals.

Environmental concentrations of tire rubber-derived 6PPD-quinone alter CNS function in zebrafish larvae.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone) is a degradation product of 6PPD, an antioxidant widely used in rubber tires. 6PPD-quinone enters aquatic ecosystems through urban stormwater runoff and has been identified as the chemical behind the urban runoff mortality syndrome in coho salmon. However, the available data suggest that the acute effects of 6PPD-quinone are restricted to a few salmonid species and that the environmental levels of this chemical should be safe for most fish.

Heart rate and behavioral responses in three phylogenetically distant aquatic model organisms exposed to environmental concentrations of carbaryl and fenitrothion.

Carbaryl and fenitrothion are two insecticides sharing a common mode of action, the inhibition of the acetylcholinesterase (AChE) activity. Their use is now regulated or banned in different countries, and the environmental levels of both compounds in aquatic ecosystems have decreased to the range of pg/L to ng/L. As these concentrations are below the non-observed-adverse-effect-concentrations (NOAEC) for AChE inhibition reported for both compounds in aquatic organisms, there is a general agreement that the current levels of these two chemicals are safe for aquatic organisms.

Environmental levels of carbaryl impair zebrafish larvae behaviour: The potential role of ADRA2B and HTR2B.

The insecticide carbaryl is commonly found in indirectly exposed freshwater ecosystems at low concentrations considered safe for fish communities. In this study, we showed that after only 24 h of exposure to environmental concentrations of carbaryl (0.066-660 ng/L), zebrafish larvae exhibit impairments in essential behaviours.

A Zebrafish Model of Neurotoxicity by Binge-Like Methamphetamine Exposure.

Hyperthermia is a common confounding factor for assessing the neurotoxic effects of methamphetamine (METH) in mammalian models. The development of new models of methamphetamine neurotoxicity using vertebrate poikilothermic animals should allow to overcome this problem. The aim of the present study was to develop a zebrafish model of neurotoxicity by binge-like methamphetamine exposure.

Pharmacological modulation of fish-induced depth selection in D. magna: the role of cholinergic and GABAergic signalling.

Animal behaviour is closely related to individual fitness, which allows animals to choose suitable mates or avoid predation. The central nervous system regulates many aspects of animal behaviour responses. Therefore, behavioural responses can be especially sensitive to compounds with a neurodevelopmental or neurofunctional mode of action.

Androgenic activation, impairment of the monoaminergic system and altered behavior in zebrafish larvae exposed to environmental concentrations of fenitrothion.

Fenitrothion is an organophosphorus insecticide usually found in aquatic ecosystems at concentrations in the range of low ng/L. In this manuscript we show that 24 h exposure to environmental concentrations of fenitrothion, from ng/L to low μg/L, altered basal locomotor activity, visual-motor response and acoustic/vibrational escape response of zebrafish larvae. Furthermore, fenitrothion and expression of gap43a, gfap, atp2b1a, and mbp exhibited a significant non-monotonic concentration-response relationship.

A high-throughput assay for screening environmental pollutants and drugs impairing predator avoidance in Daphnia magna.

This study addresses short-term habituation of the escape response in the aquatic crustacean Daphnia magna evoked by sudden changes in light intensity, using a high-throughput system. Daphnia magna exhibits a marked phototactic behaviour and swim away from light to avoid predation by fish. Currently, there is no information available on the habituation of this phototactic response.

Publisher Correction: Therapeutic potential of N-acetylcysteine in acrylamide acute neurotoxicity in adult zebrafish.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Therapeutic potential of N-acetylcysteine in acrylamide acute neurotoxicity in adult zebrafish.

Two essential key events in acrylamide (ACR) acute neurotoxicity are the formation of adducts with nucleophilic sulfhydryl groups on cysteine residues of selected proteins in the synaptic terminals and the depletion of the glutathione (GSx) stores in neural tissue. The use of N-acetylcysteine (NAC) has been recently proposed as a potential antidote against ACR neurotoxicity, as this chemical is not only a well-known precursor of the reduced form of glutathione (GSH), but also is an scavenger of soft electrophiles such as ACR. In this study, the suitability of 0.

Deciphering the mode of action of pollutants impairing the fish larvae escape response with the vibrational startle response assay.

The escape response evoked by vibrational stimuli and its habituation, essential behaviors for fish larvae survival, can be altered by neurotoxic environmental pollutants commonly found in our aquatic ecosystems. In this study we have analyzed the suitability of the Vibrational Startle Response Assay (VSRA) to obtain mechanistic information about the mode of action (MoA) of the chemicals impairing the escape response and its habituation. As a proof of concept, the pathophysiological mechanisms behind the action of two common neurotoxic pesticides, chlorpyrifos-oxon (CPO) and imidacloprid, over their effects on arousal and habituation of the escape response were studied by using pharmacological antagonists of the nicotinic and muscarinic acetylcholine receptors, mecamylamine (MCA) and scopolamine, respectively.

Development of a vibrational startle response assay for screening environmental pollutants and drugs impairing predator avoidance.

The present paper describes the vibrational startle response assay (VSRA), a new robust, simple and automated in vivo medium- to high-throughput procedure for assessment of the escape response and its habituation in zebrafish larvae. Such behaviors enable fish larvae to escape from predator strikes in aquatic ecosystems. The assay is based on measuring the distance moved by each larva during the startle response evoked by repetitive vibrational stimuli.