PUBLICATION
Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model
- Authors
- Panlilio, J.M., Aluru, N., Hahn, M.E.
- ID
- ZDB-PUB-201120-28
- Date
- 2020
- Source
- Environmental health perspectives 128: 117002 (Journal)
- Registered Authors
- Hahn, Mark E., Panlilio, Jennifer Martinez
- Keywords
- none
- Datasets
- GEO:GSE140045
- MeSH Terms
-
- Animals
- Behavior, Animal/drug effects*
- Harmful Algal Bloom
- Kainic Acid/analogs & derivatives*
- Kainic Acid/toxicity
- Nervous System/drug effects*
- Neurotoxicity Syndromes/veterinary
- Water Pollutants, Chemical/toxicity*
- Zebrafish/physiology
- PubMed
- 33147070 Full text @ Environ. Health Perspect.
- CTD
- 33147070
Citation
Panlilio, J.M., Aluru, N., Hahn, M.E. (2020) Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model. Environmental health perspectives. 128:117002.
Abstract
Background Harmful algal blooms (HABs) produce potent neurotoxins that threaten human health, but current regulations may not be protective of sensitive populations. Early life exposure to low levels of the HAB toxin domoic acid (DomA) produces long-lasting behavioral deficits in rodent and primate models; however, the mechanisms involved are unknown. The zebrafish is a powerful in vivo vertebrate model system for exploring cellular processes during development and thus may help to elucidate mechanisms of DomA developmental neurotoxicity.
Objectives We used the zebrafish model to investigate how low doses of DomA affect the developing nervous system, including windows of susceptibility to DomA exposure, structural and molecular changes in the nervous system, and the link to behavioral alterations.
Methods To identify potential windows of susceptibility, DomA (0.09 - 0.18 ng
Results Larvae exposed to DomA at 2 d postfertilization (dpf), but not at 1 or 4 dpf, showed consistent deficits in startle behavior at 7 dpf, including lower responsiveness and altered kinematics. Similarly, myelination in the spinal cord was disorganized after exposure at 2 dpf but not 1 or 4 dpf. Time-lapse imaging revealed disruption of the initial stages of myelination. DomA exposure at 2 dpf down-regulated genes required for maintaining myelin structure and the axonal cytoskeleton.
Discussion These results in zebrafish reveal a developmental window of susceptibility to DomA-induced behavioral deficits and identify altered gene expression and disrupted myelin structure as possible mechanisms. The results establish a zebrafish model for investigating the mechanisms of developmental DomA toxicity, including effects with potential relevance to exposed sensitive human populations. https://doi.org/10.1289/EHP6652.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping