PUBLICATION
Zebrafish as a Model Organism to Study Neurotoxicity: A Potential Tool for Neuroprotective Drug Discovery
- Authors
- Kumar, R., Dhiman, P., Singh, D.
- ID
- ZDB-PUB-260316-31
- Date
- 2026
- Source
- Current drug metabolism : (Journal)
- Registered Authors
- Keywords
- Acetylcholinesterase, Danio rerio, cognitive deficits, excitotoxicity, locomotor deficits, neurotoxicity.
- MeSH Terms
- none
- PubMed
- 41832725 Full text @ Curr. Drug Metab.
Citation
Kumar, R., Dhiman, P., Singh, D. (2026) Zebrafish as a Model Organism to Study Neurotoxicity: A Potential Tool for Neuroprotective Drug Discovery. Current drug metabolism. :. Epub ahead of print.
Abstract
Introduction Danio rerio, the zebrafish, serves as an excellent model in neuroprotective drug discovery due to its conserved nervous system organization, neurotransmitter pathways, antioxidant de-fenses, and genomic similarity to mammals.
Methods A systematic literature search following PRISMA 2020 guidelines was conducted across Pub-Med, Scopus, Web of Science, and Google Scholar. Studies published between 2020 and 2025 were pri-oritized, with earlier key papers included for context. The data on larval, adult, and genetically modified zebrafish models were analyzed for neurotoxic effects, focusing on study design, toxicants, and neurobe-havioral or molecular outcomes.
Results Neurotoxicants such as chlorpyrifos, bisphenol, triphenyl phosphate, aluminum, ammonium ac-etate, arsenic, zinc, acrylamide, methylmercury, and tris (1,3-dichloro-2-propyl) phosphate were shown to cross the zebrafish blood-brain barrier. These exposures caused significant behavioral alterations, neu-rotransmitter imbalances, oxidative stress, and gene or protein expression changes related to brain func-tion. Analysis of the transgenic zebrafish revealed notable alterations in neuronal development and axonal morphology upon exposure to various neurotoxic chemicals.
Discussion Zebrafish display neurotoxic responses with a close resemblance to mammals, supporting their translational value in neurotoxicity and drug discovery studies. However, limitations such as a less complex brain compared to mammals, quick neuronal regeneration, limited tissue access, and difficulties in drug absorption quantification warrant refinements in zebrafish models.
Conclusion Zebrafish offer a versatile, cost-effective, and genetically tractable system for neurotoxicity and neuroprotection research. This systematic review highlights their crucial role in neuroprotective drug discovery while emphasizing the need for improved methodological approaches to enhance translational reliability.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping