scholarly journals Domoic acid disruption of neurodevelopment and behavior involves altered myelination in the spinal cord

2019 ◽  
Author(s):  
Jennifer M. Panlilio ◽  
Neelakanteswar Aluru ◽  
Mark E. Hahn

ABSTRACTHarmful algal blooms (HABs) produce potent neurotoxins that threaten human health. Early life exposure to low levels of the HAB toxin domoic acid (DomA) produces long-lasting behavioral deficits, but the mechanisms involved are unknown. Using zebrafish, we investigated the developmental window of susceptibility to low doses of DomA and examined cellular and molecular targets. Larvae exposed to DomA at 2 days post-fertilization (dpf), but not at 1 or 4 dpf, showed consistent deficits in startle behavior including reduced responsiveness and altered kinematics. Similarly, myelination in the spinal cord was disorganized after exposure only at 2 dpf. Time-lapse imaging revealed disruption of the initial stages of myelination. DomA down-regulated genes required for maintaining myelin structure and the axonal cytoskeleton. These results identify a developmental window of susceptibility to DomA-induced behavioral deficits involving altered gene expression and disrupted myelin structure, and establish a zebrafish model for investigating the underlying mechanisms.GRAPHICAL ABSTRACT

2005 ◽  
Vol 42 (2) ◽  
pp. 184-191 ◽  
Author(s):  
P. A. Silvagni ◽  
L. J. Lowenstine ◽  
T. Spraker ◽  
T. P. Lipscomb ◽  
F. M. D. Gulland

Over 100 free-ranging adult California sea lions ( Zalophus californianus) and one Northern fur seal ( Callorhinus ursinus), predominantly adult females, were intoxicated by domoic acid (DA) during three harmful algal blooms between 1998 and 2000 in central and northern California coastal waters. The vector prey item was Northern anchovy ( Engraulis mordax) and the primary DA-producing algal diatom was Psuedonitzschia australis. Postmortem examination revealed gross and histologic findings that were distinctive and aided in diagnosis. A total of 109 sea lions were examined, dying between 1 day and 10 months after admission to a marine mammal rehabilitation center. Persistent seizures with obtundation were the main clinical findings. Frequent gross findings in animals dying acutely consisted of piriform lobe malacia, myocardial pallor, bronchopneumonia, and complications related to pregnancy. Gross findings in animals dying months after intoxication included bilateral hippocampal atrophy. Histologic observations implicated limbic system seizure injury consistent with excitotoxin exposure. Peracutely, there was microvesicular hydropic degeneration within the neuropil of the hippocampus, amygdala, pyriform lobe, and other limbic structures. Acutely, there was ischemic neuronal necrosis, particularly apparent in the granular cells of the dentate gyrus and the pyramidal cells within the hippocampus cornu ammonis (CA) sectors CA4, CA3, and CA1. Dentate granular cell necrosis has not been reported in human or experimental animal DA toxicity and may be unique to sea lions. Chronically, there was gliosis, mild nonsuppurative inflammation, and loss of laminar organization in affected areas.


Science ◽  
2018 ◽  
Vol 361 (6409) ◽  
pp. 1356-1358 ◽  
Author(s):  
John K. Brunson ◽  
Shaun M. K. McKinnie ◽  
Jonathan R. Chekan ◽  
John P. McCrow ◽  
Zachary D. Miles ◽  
...  

Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA’s diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production.


Harmful Algae ◽  
2020 ◽  
Vol 96 ◽  
pp. 101799 ◽  
Author(s):  
Stephanie K. Moore ◽  
Stacia J. Dreyer ◽  
Julia A. Ekstrom ◽  
Kathleen Moore ◽  
Karma Norman ◽  
...  

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 18
Author(s):  
Sophie Guillotin ◽  
Nicolas Delcourt

Harmful algal blooms (HAB), and the consequent release of toxic metabolites, can be responsible for seafood poisoning outbreaks. Marine wildlife can accumulate these toxins throughout the food chain, which presents a threat to consumers’ health. Some of these toxins, such as saxitoxin (STX), domoic acid (DA), ciguatoxin (CTX), brevetoxin (BTX), tetrodotoxin (TTX), and β-N-methylamino-L-alanine (BMAA), cause severe neurological symptoms in humans. Considerable information is missing, however, notably the consequences of toxin exposures on changes in gene expression, protein profile, and metabolic pathways. This information could lead to understanding the consequence of marine neurotoxin exposure in aquatic organisms and humans. Nevertheless, recent contributions to the knowledge of neurotoxins arise from OMICS-based research, such as genomics, transcriptomics, proteomics, and metabolomics. This review presents a comprehensive overview of the most recent research and of the available solutions to explore OMICS datasets in order to identify new features in terms of ecotoxicology, food safety, and human health. In addition, future perspectives in OMICS studies are discussed.


2021 ◽  
Author(s):  
Jennifer M Panlilio ◽  
Ian T. Jones ◽  
Matthew C. Salanga ◽  
Neelakanteswar M Aluru ◽  
Mark E Hahn

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.


Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 903
Author(s):  
Holly Kelchner ◽  
Katie E. Reeve-Arnold ◽  
Kathryn M. Schreiner ◽  
Sibel Bargu ◽  
Kim G. Roques ◽  
...  

Harmful algal blooms (HABs) are increasing globally in frequency, persistence, and geographic extent, posing a threat to ecosystem and human health. To date, no occurrences of marine phycotoxins have been recorded in Mozambique, which may be due to absence of a monitoring program and general awareness of potential threats. This study is the first documentation of neurotoxin, domoic acid (DA), produced by the diatom Pseudo-nitzschia along the east coast of Africa. Coastal Inhambane Province is a biodiversity hotspot where year-round Rhincodon typus (whale shark) sightings are among the highest globally and support an emerging ecotourism industry. Links between primary productivity and biodiversity in this area have not previously been considered or reported. During a pilot study, from January 2017 to April 2018, DA was identified year-round, peaking during Austral winter. During an intense study between May and August 2018, our research focused on identifying environmental factors influencing coastal productivity and DA concentration. Phytoplankton assemblage was diatom-dominated, with high abundances of Pseudo-nitzschia spp. Data suggest the system was influenced by nutrient pulses resulting from coastal upwelling. Continued and comprehensive monitoring along southern Mozambique would provide critical information to assess ecosystem and human health threats from marine toxins under challenges posed by global change.


Water ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1954 ◽  
Author(s):  
Jesus M. Torres Palenzuela ◽  
Luis González Vilas ◽  
Francisco M. Bellas ◽  
Elina Garet ◽  
África González-Fernández ◽  
...  

The NW coast of the Iberian Peninsula is dominated by extensive shellfish farming, which places this region as a world leader in mussel production. Harmful algal blooms in the area frequent lead to lengthy harvesting closures threatening food security. This study developed a framework for the detection of Pseudo-nitzschia blooms in the Galician rias from satellite data (MERIS full-resolution images) and identified key variables that affect their abundance and toxicity. Two events of toxin-containing Pseudo-nitzschia were detected (up to 2.5 μg L−1 pDA) in the area. This study suggests that even moderate densities of Pseudo-nitzschia in this area might indicate high toxin content. Empirical models for particulate domoic acid (pDA) were developed based on MERIS FR data. The resulting remote-sensing model, including MERIS bands centered around 510, 560, and 620 nm explain 73% of the pDA variance (R2 = 0.73, p < 0.001). The results show that higher salinity values and lower Si(OH)4/N ratios favour higher Pseudo-nitzschia spp. abundances. High pDA values seem to be associated with relatively high PO43, low NO3− concentrations, and low Si(OH)4/N. While MERIS FR data and regionally specific algorithms can be useful for detecting Pseudo-nitzschia blooms, nutrient relationships are crucial for predicting the toxicity of these blooms.


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