Department Environmental Toxicology

ToxPathways


Some individuals are more susceptible to chemical exposure than others, but underlying reasons remain largely obscure. We are investigating these inter-individual differences to gain better understanding of the underlying causes of variability in chemical susceptibility and in addition to obtain insights in the molecular mechanism of action of environmentally relevant chemicals. To study this, we are using zebrafish behavioral assays as a method to sort chemically-exposed individuals into susceptible and tolerant categories, and subsequently analyze their molecular profiles. Zebrafish locomotor behavior can serve as an indicator of perturbations in the nervous system and can be assessed conveniently in a standard well-plate for a large number of larvae simultaneously. Moreover, major brain structures and physiological processes are conserved among phyla, allowing not only neuroactive substances (pharmaceuticals, pesticides etc.) to be analyzed, but also basic findings to be translated to other species, such as other teleosts, and to some extent to vertebrates in general. This project aims to elucidate toxicological response pathways at the molecular level, a much needed basis for a proper risk assessment of contaminants in the aquatic environment, and in turn might potentially identify new contaminant specific biomarkers.

Publications

Approaches to test the neurotoxicity of environmental contaminants in the zebrafish model - from behavior to molecular mechanisms

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 omitting whole animal responses. In recent years, zebrafish (Danio rerio) have become a popular model organism for toxicological studies and testing strategies, such as the standardized use of zebrafish early life stages in the OECD 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.
Fitzgerald, J. A.; Könemann, S.; Krümpelmann, L.; Županič, A.; vom Berg, C. (2021) Approaches to test the neurotoxicity of environmental contaminants in the zebrafish model - from behavior to molecular mechanisms, Environmental Toxicology and Chemistry, 40(4), 989-1006, doi:10.1002/etc.4951, Institutional Repository

Emergence of consistent intra-individual locomotor patterns during zebrafish development

The analysis of larval zebrafish locomotor behavior has emerged as a powerful indicator of perturbations in the nervous system and is used in many fields of research, including neuroscience, toxicology and drug discovery. The behavior of larval zebrafish however, is highly variable, resulting in the use of large numbers of animals and the inability to detect small effects. In this study, we analyzed whether individual locomotor behavior is stable over development and whether behavioral parameters correlate with physiological and morphological features, with the aim of better understanding the variability and predictability of larval locomotor behavior. Our results reveal that locomotor activity of an individual larva remains consistent throughout a given day and is predictable throughout larval development, especially during dark phases, under which larvae demonstrate light-searching behaviors and increased activity. The larvae’s response to startle-stimuli was found to be unpredictable, with no correlation found between response strength and locomotor activity. Furthermore, locomotor activity was not associated with physiological or morphological features of a larva (resting heart rate, body length, size of the swim bladder). Overall, our findings highlight the areas of intra-individual consistency, which could be used to improve the sensitivity of assays using zebrafish locomotor activity as an endpoint.
Fitzgerald, J. A.; Kirla, K. T.; Zinner, C. P.; vom Berg, C. M. (2019) Emergence of consistent intra-individual locomotor patterns during zebrafish development, Scientific Reports, 9, 13647 (14 pp.), doi:10.1038/s41598-019-49614-y, Institutional Repository

Contact (PI)

Dr. Colette vom Berg Deputy head of department Tel. +41 58 765 5535 Send Mail

In collaboration with

Carl Zinner

Former team member

Dr. Krishna Tulasi Kirla
Dr. Jennifer Fitzgerald

Funding

Eawag Discretionary Fund