Impacts of developmental exposures to the harmful algal bloom toxin domoic acid on neural development and behavior

Panlilio, Jennifer M.

doi:10.1575/1912/24081

Cited by 2 publications

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“…Alternatively, DomA may perturb oligodendrocyte development and myelin wrapping, leading to later axonal dysfunction. Further work is underway to investigate the potential axonal targets of DomA toxicity and to assess the contribution of the axonal disruptions to the myelin sheath phenotypes that we characterized here (Panlilio 2019). RNA-seq data showed higher expression of glial fibrillary acidic protein (gfap) in DomA-exposed fish relative to controls.…”

Section: Doma-induced Transcriptional Changesmentioning

confidence: 94%

Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model

Panlilio

Aluru

Hahn

2020

Environ Health Perspect

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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) was delivered to zebrafish through caudal vein microinjection during distinct periods in early neurodevelopment. Following exposure, structural and molecular targets were identified using live imaging of transgenic fish and RNA sequencing. To assess the functional consequences of exposures, we quantified startle behavior in response to acoustic/vibrational stimuli. 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.

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Section: Doma-induced Transcriptional Changesmentioning

confidence: 94%

Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model

Panlilio

Aluru

Hahn

2020

Environ Health Perspect

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“…Brun and L. Kerr for microscopy training and advice (MBL microscopy facility). We also thank the labs who generously provided us with (Panlilio, 2019)…”

Section: Acknowledgementsmentioning

confidence: 99%

“…J.M.P. in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Oceanography and Applied Ocean Science and Engineering at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution (Panlilio, 2019)…”

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Developmental exposure to domoic acid disrupts startle response behavior and circuitry

Panlilio

Jones

Salanga

et al. 2021

Preprint

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Harmful algal blooms produce potent neurotoxins that accumulate in seafood and are hazardous to human health. Developmental exposure to the harmful algal bloom toxin, domoic acid (DomA), has behavioral consequences well into adulthood, but the cellular and molecular mechanisms are largely unknown. To assess these, we exposed zebrafish embryos to DomA during the previously identified window of susceptibility (2 days post-fertilization) and used the well-known startle response circuit as a tool to identify specific neuronal components that are targeted by exposure to DomA. Exposure to DomA reduced the probability of eliciting a startle after auditory/vibrational or electrical stimuli and led to the dramatic reduction of one type of startle, short latency c-start (SLC) responses. Furthermore, DomA-exposed larvae had altered kinematics of both SLC and long latency c-start (LLC) startle responses, exhibiting shallower bend angles and slower maximal angular velocities. Using vital dye staining, immunolabelling, and live imaging of transgenic lines, we determined that while the sensory inputs were intact, the reticulospinal neurons required for SLC responses were absent in most DomA-exposed larvae. Furthermore, axon tracing revealed that DomA-treated larvae also showed significantly reduced primary motor neuron axon collaterals. Overall, these results show that developmental exposure to DomA leads to startle deficits by targeting specific subsets of neurons. These findings provide mechanistic insights into the neurodevelopmental effects of excess glutamatergic signaling caused by exposure to DomA. It further provides a model for using the startle response circuit to identify neuronal populations targeted by toxin or toxicant exposures.Summary statementWe used the zebrafish startle response as a tool to identify sensory-motor deficits and the loss of specific neural populations after developmental exposure to the harmful algal bloom toxin domoic acid.GRAPHICAL ABSTRACT

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Impacts of developmental exposures to the harmful algal bloom toxin domoic acid on neural development and behavior

Cited by 2 publications

References 0 publications

Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model

Developmental Neurotoxicity of the Harmful Algal Bloom Toxin Domoic Acid: Cellular and Molecular Mechanisms Underlying Altered Behavior in the Zebrafish Model

Developmental exposure to domoic acid disrupts startle response behavior and circuitry

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