Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms

Abstract

The occurrence of neuroactive chemicals in the aquatic environment is on the rise and poses a potential threat to aquatic biota of currently unpredictable outcome. In particular, subtle changes caused by these chemicals to an organism's sensation or behavior are difficult to tackle with current test systems that focus on rodents or with in vitro test systems that omit whole-animal responses. In recent years, the zebrafish (Danio rerio) has become a popular model organism for toxicological studies and testing strategies, such as the standardized use of zebrafish early life stages in the Organisation for Economic Cooperation and Development's guideline 236. In terms of neurotoxicity, the zebrafish provides a powerful model to investigate changes to the nervous system from several different angles, offering the ability to tackle the mechanisms of action of chemicals in detail. The mechanistic understanding gained through the analysis of this model species provides a good basic knowledge of how neuroactive chemicals might interact with a teleost nervous system. Such information can help infer potential effects occurring to other species exposed to neuroactive chemicals in their aquatic environment and predicting potential risks of a chemical for the aquatic ecosystem. In the present article, we highlight approaches ranging from behavioral to structural, functional, and molecular analysis of the larval zebrafish nervous system, providing a holistic view of potential neurotoxic outcomes.

Di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) alters transcriptional profiles, lipid metabolism and behavior in zebrafish larvae

“…It offers several advantages including easy handling, small size, and transparent body that allows for continuous visualization of developmental changes ( Bailey et al., 2013 ). The latter characteristic is particularly important to assess structural integrity of zebrafish as well as its functional ability that can be used to determine the impact of chemicals on behavior ( Bailey et al., 2013 ; Fitzgerald et al., 2020 ). Besides, it shares a higher genetic similarity with human, as around 70% of human genes have at least one ortholog in zebrafish ( Howe et al., 2013 ).…”

Sub-Lethal Peak Exposure to Insecticides Triggers Olfaction-Mediated Avoidance in Zebrafish Larvae

“…Based on the results of the present study, it has to be further investigated whether the absence of a behavioral response for some insecticides was because they were not detected or rather because they were interpreted as not adverse. To do so, the activation of sensory neurons by the respective substance could be investigated in future studies involving two-photon calcium imaging of the olfactory bulb and EOG recordings. , In addition, our future projects will use the established setup to assess the behavioral responses of fish to lower concentrations, mixtures, or environmental samples in order to mimic environmental scenarios even more closely, thereby further increasing the environmental relevance.…”

“…To do so, the activation of sensory neurons by the respective substance could be investigated in future studies involving two-photon calcium imaging of the olfactory bulb and EOG recordings. 87,88 In addition, our future projects will use the established setup to assess the behavioral responses of fish to lower concentrations, mixtures, or environmental samples in order to mimic environmental scenarios even more closely, thereby further increasing the environmental relevance.…”

Developmental Neurotoxicity and Behavioral Screening in Larval Zebrafish with a Comparison to Other Published Results

“…Moreover, zebrafish at all developmental stages metabolize toxic chemicals using pathways similar to mammals [ 21 , 22 ]. Because of these attributes, zebrafish are often proffered as a model for developmental neurotoxicity screening (reviewed in [ 23 , 24 , 25 ]).…”