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

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.

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

10.1575/1912/24081 ◽

2019 ◽

Author(s):

Jennifer M. Panlilio

Keyword(s):

Neural Development ◽

Domoic Acid ◽

Algal Bloom ◽

Harmful Algal Bloom ◽

And Behavior ◽

Developmental Exposures

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Faculty Opinions recommendation of The Haber Bosch–harmful algal bloom (HB–HAB) link.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727352837.793529170 ◽

2017 ◽

Author(s):

Hans Paerl

Keyword(s):

Algal Bloom ◽

Harmful Algal Bloom

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Comparative transcriptome and cross-section analyses provide insights into the mechanisms underlying Sargassum fusiforme responses to the harmful algal bloom-forming dinoflagellate Karenia mikimotoi

Aquatic Botany ◽

10.1016/j.aquabot.2021.103383 ◽

2021 ◽

pp. 103383

Author(s):

Lidong Lin ◽

Binbin Chen ◽

Shengqin Wang ◽

Jun Li ◽

Zengling Ma

Keyword(s):

Cross Section ◽

Algal Bloom ◽

Harmful Algal Bloom ◽

Comparative Transcriptome ◽

Sargassum Fusiforme ◽

Karenia Mikimotoi

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sxtA4+ and sxtA4- Genotypes Occur Together within Natural Pyrodinium bahamense Sub-Populations from the Western Atlantic

Microorganisms ◽

10.3390/microorganisms9061128 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1128

Author(s):

Kathleen Cusick ◽

Gabriel Duran

Keyword(s):

Molecular Mechanisms ◽

Harmful Algal Bloom ◽

Single Cells ◽

Natural Populations ◽

Indian River Lagoon ◽

Toxin Production ◽

Genotype Frequency ◽

Rrna Gene ◽

Western Atlantic ◽

Pyrodinium Bahamense

Saxitoxin (STX) is a secondary metabolite and potent neurotoxin produced by several genera of harmful algal bloom (HAB) marine dinoflagellates. The basis for variability in STX production within natural bloom populations is undefined as both toxic and non-toxic strains (of the same species) have been isolated from the same geographic locations. Pyrodinium bahamense is a STX-producing bioluminescent dinoflagellate that blooms along the east coast of Florida as well as the bioluminescent bays in Puerto Rico (PR), though no toxicity reports exist for PR populations. The core genes in the dinoflagellate STX biosynthetic pathway have been identified, and the sxtA4 gene is essential for toxin production. Using sxtA4 as a molecular proxy for the genetic capacity of STX production, we examined sxtA4+ and sxtA4- genotype frequency at the single cell level in P. bahamense populations from different locations in the Indian River Lagoon (IRL), FL, and Mosquito Bay (MB), a bioluminescent bay in PR. Multiplex PCR was performed on individual cells with Pyrodinium-specific primers targeting the 18S rRNA gene and sxtA4. The results reveal that within discrete natural populations of P. bahamense, both sxtA4+ and sxtA4- genotypes occur, and the sxtA4+ genotype dominates. In the IRL, the frequency of the sxtA4+ genotype ranged from ca. 80–100%. In MB, sxtA4+ genotype frequency ranged from ca 40–66%. To assess the extent of sxtA4 variation within individual cells, sxtA4 amplicons from single cells representative of the different sampling sites were cloned and sequenced. Overall, two variants were consistently obtained, one of which is likely a pseudogene based on alignment with cDNA sequences. These are the first data demonstrating the existence of both genotypes in natural P. bahamense sub-populations, as well as sxtA4 presence in P. bahamense from PR. These results provide insights on underlying genetic factors influencing the potential for toxin variability among natural sub-populations of HAB species and highlight the need to study the genetic diversity within HAB sub-populations at a fine level in order to identify the molecular mechanisms driving HAB evolution.

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