Marine Neurotoxins

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (15 December 2016) | Viewed by 191771

Special Issue Editor


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Guest Editor
Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Box 354695, Suite 100, 4225 Roosevelt Way NE, Seattle, WA 98195, USA
Interests: neurotoxicology

Special Issue Information

Dear Colleagues,

Many marine biotoxins, such as domoic acid, palytoxin, ciguatera toxin, saxitoxin, and tetrodotoxin are produced by phytoplankton and some species of invertebrates and fish. These marine biotoxins can affect neurological functions, so as to induce health risks or even death. In this Special Issue, we explore the mechanisms and factors affecting neurotoxicity and look at gene-environment interactions, developmental neurotoxicity, and age-dependent neurotoxicity through marine neurotoxin research. We also welcome papers concerning marine neurotoxins as experimental models, potential therapeutics or neurobiological tools, as well as studies investigating the relationship between marine toxins and neurodegenerative diseases and the development of biosensors for neurotoxin detection. As guest editor of this Special Issue, I invite you to submit reviews, research articles or communications in this exciting field.

Prof. Dr. Lucio G. Costa
Guest Editor

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Keywords

  • domoic acid
  • palytoxin
  • ciguatera toxin
  • saxitoxin
  • tetrodotoxin
  • mechanisms of neurotoxicity
  • factors affecting neurotoxicity
  • gene-environment interactions
  • developmental neurotoxicity
  • age-dependent neurotoxicity
  • marine neurotoxins as experimental models
  • marine neurotoxins as potential therapeutics
  • marine neurotoxins as neurobiological tools
  • neurodegenerative diseases
  • biosensors for marine neurotoxins

 

 

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Published Papers (17 papers)

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Research

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2371 KiB  
Article
Seasonal Changes in the Tetrodotoxin Content of the Flatworm Planocera multitentaculata
by Riko Yamada, Tadasuke Tsunashima, Mitsuki Takei, Tatsunori Sato, Yoshiki Wajima, Makoto Kawase, Shotaro Oshikiri, Yusuke Kajitani, Keita Kosoba, Hiroyuki Ueda, Koko Abe, Shiro Itoi and Haruo Sugita
Mar. Drugs 2017, 15(3), 56; https://doi.org/10.3390/md15030056 - 25 Feb 2017
Cited by 24 | Viewed by 7664
Abstract
Tetrodotoxin (TTX) is a potent neurotoxin that acts specifically on voltage-gated sodium channels on excitable membranes of muscle and nerve tissues. The biosynthetic process for TTX is unclear, although marine bacteria are generally thought to be the primary producers. The marine flatworm Planocera [...] Read more.
Tetrodotoxin (TTX) is a potent neurotoxin that acts specifically on voltage-gated sodium channels on excitable membranes of muscle and nerve tissues. The biosynthetic process for TTX is unclear, although marine bacteria are generally thought to be the primary producers. The marine flatworm Planocera multitentaculata is a known TTX-bearing organism, and is suspected to be a TTX supplier to pufferfish. In this study, flatworm specimens were collected from an intertidal zone in Hayama, Kanagawa, Japan, the TTX content of the flatworm was measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and seasonal changes in TTX content were investigated. No significant difference in TTX concentration of the flatworm body was found between the spawning period and other periods. However, the TTX content in individual flatworms was significantly higher in the spawning period than at other times. The TTX content rose in association with an increase in the body weight of the flatworm. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Molecular Characterization of Voltage-Gated Sodium Channels and Their Relations with Paralytic Shellfish Toxin Bioaccumulation in the Pacific Oyster Crassostrea gigas
by Floriane Boullot, Justine Castrec, Adeline Bidault, Natanael Dantas, Laura Payton, Mickael Perrigault, Damien Tran, Zouher Amzil, Pierre Boudry, Philippe Soudant, Hélène Hégaret and Caroline Fabioux
Mar. Drugs 2017, 15(1), 21; https://doi.org/10.3390/md15010021 - 19 Jan 2017
Cited by 14 | Viewed by 7490
Abstract
Paralytic shellfish toxins (PST) bind to voltage-gated sodium channels (Nav) and block conduction of action potential in excitable cells. This study aimed to (i) characterize Nav sequences in Crassostrea gigas and (ii) investigate a putative relation between Nav and PST-bioaccumulation in oysters. The [...] Read more.
Paralytic shellfish toxins (PST) bind to voltage-gated sodium channels (Nav) and block conduction of action potential in excitable cells. This study aimed to (i) characterize Nav sequences in Crassostrea gigas and (ii) investigate a putative relation between Nav and PST-bioaccumulation in oysters. The phylogenetic analysis highlighted two types of Nav in C. gigas: a Nav1 (CgNav1) and a Nav2 (CgNav2) with sequence properties of sodium-selective and sodium/calcium-selective channels, respectively. Three alternative splice transcripts of CgNav1 named A, B and C, were characterized. The expression of CgNav1, analyzed by in situ hybridization, is specific to nervous cells and to structures corresponding to neuromuscular junctions. Real-time PCR analyses showed a strong expression of CgNav1A in the striated muscle while CgNav1B is mainly expressed in visceral ganglia. CgNav1C expression is ubiquitous. The PST binding site (domain II) of CgNav1 variants possess an amino acid Q that could potentially confer a partial saxitoxin (STX)-resistance to the channel. The CgNav1 genotype or alternative splicing would not be the key point determining PST bioaccumulation level in oysters. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
New Typical Vector of Neurotoxin β-N-Methylamino-l-Alanine (BMAA) in the Marine Benthic Ecosystem
by Aifeng Li, Jialiang Song, Yang Hu, Longji Deng, Ling Ding and Meihui Li
Mar. Drugs 2016, 14(11), 202; https://doi.org/10.3390/md14110202 - 4 Nov 2016
Cited by 24 | Viewed by 7254
Abstract
The neurotoxin β-N-methylamino-l-alanine (BMAA) has been identified as an environmental factor triggering neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD). We investigated the possible vectors of BMAA and its isomers 2,4-diaminobutyric acid (DAB) and N [...] Read more.
The neurotoxin β-N-methylamino-l-alanine (BMAA) has been identified as an environmental factor triggering neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s disease (AD). We investigated the possible vectors of BMAA and its isomers 2,4-diaminobutyric acid (DAB) and N-2(aminoethyl)glycine (AEG) in marine mollusks collected from the Chinese coast. Sixty-eight samples of marine mollusks were collected along the Chinese coast in 2016, and were analyzed by an HILIC-MS/MS (hydrophilic interaction liquid chromatography with tandem quadrupole mass spectrometer) method without derivatization. BMAA was detected in a total of five samples from three species: Neverita didyma, Solen strictus, and Mytilus coruscus. The top three concentrations of free-form BMAA (0.99~3.97 μg·g−1 wet weight) were detected in N. didyma. DAB was universally detected in most of the mollusk samples (53/68) with no species-specific or regional differences (0.051~2.65 μg·g−1 wet weight). No AEG was detected in any mollusk samples tested here. The results indicate that the gastropod N. didyma might be an important vector of the neurotoxin BMAA in the Chinese marine ecosystem. The neurotoxin DAB was universally present in marine bivalve and gastropod mollusks. Since N. didyma is consumed by humans, we suggest that the origin and risk of BMAA and DAB toxins in the marine ecosystem should be further investigated in the future. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
A Collaborative Evaluation of LC-MS/MS Based Methods for BMAA Analysis: Soluble Bound BMAA Found to Be an Important Fraction
by Elisabeth J. Faassen, Maria G. Antoniou, Wendy Beekman-Lukassen, Lucie Blahova, Ekaterina Chernova, Christophoros Christophoridis, Audrey Combes, Christine Edwards, Jutta Fastner, Joop Harmsen, Anastasia Hiskia, Leopold L. Ilag, Triantafyllos Kaloudis, Srdjan Lopicic, Miquel Lürling, Hanna Mazur-Marzec, Jussi Meriluoto, Cristina Porojan, Yehudit Viner-Mozzini and Nadezda Zguna
Mar. Drugs 2016, 14(3), 45; https://doi.org/10.3390/md14030045 - 29 Feb 2016
Cited by 51 | Viewed by 10442
Abstract
Exposure to β-N-methylamino-l-alanine (BMAA) might be linked to the incidence of amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson’s disease. Analytical chemistry plays a crucial role in determining human BMAA exposure and the associated health risk, but the performance of [...] Read more.
Exposure to β-N-methylamino-l-alanine (BMAA) might be linked to the incidence of amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson’s disease. Analytical chemistry plays a crucial role in determining human BMAA exposure and the associated health risk, but the performance of various analytical methods currently employed is rarely compared. A CYANOCOST initiated workshop was organized aimed at training scientists in BMAA analysis, creating mutual understanding and paving the way towards interlaboratory comparison exercises. During this workshop, we tested different methods (extraction followed by derivatization and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis, or directly followed by LC-MS/MS analysis) for trueness and intermediate precision. We adapted three workup methods for the underivatized analysis of animal, brain and cyanobacterial samples. Based on recovery of the internal standard D3BMAA, the underivatized methods were accurate (mean recovery 80%) and precise (mean relative standard deviation 10%), except for the cyanobacterium Leptolyngbya. However, total BMAA concentrations in the positive controls (cycad seeds) showed higher variation (relative standard deviation 21%–32%), implying that D3BMAA was not a good indicator for the release of BMAA from bound forms. Significant losses occurred during workup for the derivatized method, resulting in low recovery (<10%). Most BMAA was found in a trichloroacetic acid soluble, bound form and we recommend including this fraction during analysis. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Algal Toxin Azaspiracid-1 Induces Early Neuronal Differentiation and Alters Peripherin Isoform Stoichiometry
by Linda V. Hjørnevik, Ann K. Frøyset, Toril A. Grønset, Krisna Rungruangsak-Torrissen and Kari E. Fladmark
Mar. Drugs 2015, 13(12), 7390-7402; https://doi.org/10.3390/md13127072 - 14 Dec 2015
Cited by 9 | Viewed by 6018
Abstract
Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to [...] Read more.
Azaspiracid-1 is an algal toxin that accumulates in edible mussels, and ingestion may result in human illness as manifested by vomiting and diarrhoea. When injected into mice, it causes neurotoxicological symptoms and death. Although it is well known that azaspiracid-1 is toxic to most cells and cell lines, little is known about its biological target(s). A rat PC12 cell line, commonly used as a model for the peripheral nervous system, was used to study the neurotoxicological effects of azaspiracid-1. Azaspiracid-1 induced differentiation-related morphological changes followed by a latter cell death. The differentiated phenotype showed peripherin-labelled neurite-like processes simultaneously as a specific isoform of peripherin was down-regulated. The precise mechanism behind this down-regulation remains uncertain. However, this study provides new insights into the neurological effects of azaspiracid-1 and into the biological significance of specific isoforms of peripherin. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Hunt for Palytoxins in a Wide Variety of Marine Organisms Harvested in 2010 on the French Mediterranean Coast
by Ronel Biré, Sophie Trotereau, Rodolphe Lemée, Davide Oregioni, Christine Delpont, Sophie Krys and Thierry Guérin
Mar. Drugs 2015, 13(8), 5425-5446; https://doi.org/10.3390/md13085425 - 21 Aug 2015
Cited by 38 | Viewed by 6462
Abstract
During the summer of 2010, 31 species including fish, echinoderms, gastropods, crustaceans, cephalopods and sponges were sampled in the Bay of Villefranche on the French Mediterranean coast and screened for the presence of PLTX-group toxins using the haemolytic assay. Liquid chromatography tandem mass [...] Read more.
During the summer of 2010, 31 species including fish, echinoderms, gastropods, crustaceans, cephalopods and sponges were sampled in the Bay of Villefranche on the French Mediterranean coast and screened for the presence of PLTX-group toxins using the haemolytic assay. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for confirmatory purposes and to determine the toxin profile. The mean toxin concentration in the whole flesh of all sampled marine organisms, determined using the lower- (LB) and upper-bound (UB) approach was 4.3 and 5.1 µg·kg−1, respectively, with less than 1% of the results exceeding the European Food Safety Authority (EFSA) threshold of 30 µg·kg−1and the highest values being reported for sea urchins (107.6 and 108.0 µg·kg−1). Toxins accumulated almost exclusively in the digestive tube of the tested species, with the exception of octopus, in which there were detectable toxin amounts in the remaining tissues (RT). The mean toxin concentration in the RT of the sampled organisms (fishes, echinoderms and cephalopods) was 0.7 and 1.7 µg·kg−1 (LB and UB, respectively), with a maximum value of 19.9 µg·kg−1 for octopus RT. The herbivorous and omnivorous organisms were the most contaminated species, indicating that diet influences the contamination process, and the LC-MS/MS revealed that ovatoxin-a was the only toxin detected. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Diversity and Biosynthetic Potential of Culturable Microbes Associated with Toxic Marine Animals
by Rocky Chau, John A. Kalaitzis, Susanna A. Wood and Brett A. Neilan
Mar. Drugs 2013, 11(8), 2695-2712; https://doi.org/10.3390/md11082695 - 2 Aug 2013
Cited by 31 | Viewed by 9173
Abstract
Tetrodotoxin (TTX) is a neurotoxin that has been reported from taxonomically diverse organisms across 14 different phyla. The biogenic origin of tetrodotoxin is still disputed, however, TTX biosynthesis by host-associated bacteria has been reported. An investigation into the culturable microbial populations from the [...] Read more.
Tetrodotoxin (TTX) is a neurotoxin that has been reported from taxonomically diverse organisms across 14 different phyla. The biogenic origin of tetrodotoxin is still disputed, however, TTX biosynthesis by host-associated bacteria has been reported. An investigation into the culturable microbial populations from the TTX-associated blue-ringed octopus Hapalochlaena sp. and sea slug Pleurobranchaea maculata revealed a surprisingly high microbial diversity. Although TTX was not detected among the cultured isolates, PCR screening identifiedsome natural product biosynthesis genes putatively involved in its assembly. This study is the first to report on the microbial diversity of culturable communities from H. maculosa and P. maculata and common natural product biosynthesis genes from their microbiota. We also reassess the production of TTX reported from three bacterial strains isolated from the TTX-containing gastropod Nassarius semiplicatus. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Influence of Environmental Factors on the Paralytic Shellfish Toxin Content and Profile of Alexandrium catenella (Dinophyceae) Isolated from the Mediterranean Sea
by Mohamed Laabir, Yves Collos, Estelle Masseret, Daniel Grzebyk, Eric Abadie, Véronique Savar, Manoella Sibat and Zouher Amzil
Mar. Drugs 2013, 11(5), 1583-1601; https://doi.org/10.3390/md11051583 - 15 May 2013
Cited by 67 | Viewed by 10654
Abstract
Laboratory experiments were designed to study the toxin content and profile of the Alexandrium catenella strain ACT03 (isolated from Thau Lagoon, French Mediterranean) in response to abiotic environmental factors under nutrient-replete conditions. This dinoflagellate can produce various paralytic shellfish toxins with concentrations ranging [...] Read more.
Laboratory experiments were designed to study the toxin content and profile of the Alexandrium catenella strain ACT03 (isolated from Thau Lagoon, French Mediterranean) in response to abiotic environmental factors under nutrient-replete conditions. This dinoflagellate can produce various paralytic shellfish toxins with concentrations ranging from 2.9 to 50.3 fmol/cell. The toxin profile was characterized by carbamate toxins (GTX3, GTX4 and GTX5) and N-sulfocarbamoyl toxins (C1, C2, C3 and C4). C2 dominated at 12–18 °C, but only for salinities ranging from 10 to 25 psu, whereas GTX5 became dominant at temperatures ranging from 21 to 30 °C at almost all salinities. There was no significant variation in the cellular toxin amount from 18 °C to 27 °C for salinities ranging between 30 and 40 psu. At salinities of 10 to 25 psu, the toxin concentrations always remained below 20 fmol/cell. Toxin content was stable for irradiance ranging from 10 to 70 μmol photons/m2/s then slightly increased. Overall, the toxin profile was more stable than the toxin content (fmol/cell), except for temperature and/or salinity values different from those recorded during Alexandrium blooms in Thau Lagoon. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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597 KiB  
Article
A Conus regularis Conotoxin with a Novel Eight-Cysteine Framework Inhibits CaV2.2 Channels and Displays an Anti-Nociceptive Activity
by Johanna Bernáldez, Sergio A. Román-González, Oscar Martínez, Samanta Jiménez, Oscar Vivas, Isabel Arenas, Gerardo Corzo, Roberto Arreguín, David E. García, Lourival D. Possani and Alexei Licea
Mar. Drugs 2013, 11(4), 1188-1202; https://doi.org/10.3390/md11041188 - 8 Apr 2013
Cited by 28 | Viewed by 8954
Abstract
A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in the Sea of Cortez, México. Its primary structure was determined by mass spectrometry and confirmed by automated Edman degradation. This conotoxin contains 40 [...] Read more.
A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in the Sea of Cortez, México. Its primary structure was determined by mass spectrometry and confirmed by automated Edman degradation. This conotoxin contains 40 amino acids and exhibits a novel arrangement of eight cysteine residues (C-C-C-C-CC-CC). Surprisingly, two loops of the novel peptide are highly identical to the amino acids sequence of ω-MVIIA. The total length and disulfide pairing of both peptides are quite different, although the two most important residues for the described function of ω-MVIIA (Lys2 and Tyr13) are also present in the peptide reported here. Electrophysiological analysis using superior cervical ganglion (SCG) neurons indicates that RsXXIVA inhibits CaV2.2 channel current in a dose-dependent manner with an EC50 of 2.8 μM, whose effect is partially reversed after washing. Furthermore, RsXXIVA was tested in hot-plate assays to measure the potential anti-nociceptive effect to an acute thermal stimulus, showing an analgesic effect in acute thermal pain at 30 and 45 min post-injection. Also, the toxin shows an anti-nociceptive effect in a formalin chronic pain test. However, the low affinity for CaV2.2 suggests that the primary target of the peptide could be different from that of ω-MVIIA. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Improved Detection of Domoic Acid Using Covalently Immobilised Antibody Fragments
by María J. Hortigüela and J. Gerard Wall
Mar. Drugs 2013, 11(3), 881-895; https://doi.org/10.3390/md11030881 - 14 Mar 2013
Cited by 17 | Viewed by 9059
Abstract
Antibody molecules, and antibody fragments in particular, have enormous potential in the development of biosensors for marine monitoring. Conventional immobilisation approaches used in immunoassays typically yield unstable and mostly incorrectly oriented antibodies, however, resulting in reduced detection sensitivities for already low concentration analytes. [...] Read more.
Antibody molecules, and antibody fragments in particular, have enormous potential in the development of biosensors for marine monitoring. Conventional immobilisation approaches used in immunoassays typically yield unstable and mostly incorrectly oriented antibodies, however, resulting in reduced detection sensitivities for already low concentration analytes. The 2H12 anti-domoic acid scFv antibody fragment was engineered with cysteine-containing linkers of two different lengths, distal to the antigen binding pocket, for covalent and correctly oriented immobilisation of the scFvs on functionalised solid supports. The Escherichia coli-produced, cysteine-engineered scFvs dimerised in solution and demonstrated similar efficiencies of covalent immobilisation on maleimide-activated plates and minimal non-covalent attachment. The covalently attached scFvs exhibited negligible leaching from the support under acidic conditions that removed almost 50% of the adsorbed wildtype fragment, and IC50s for domoic acid of 270 and 297 ng/mL compared with 1126 and 1482 ng/mL, respectively, for their non-covalently adsorbed counterparts. The expression and immobilisation approach will facilitate the development of stable, reusable biosensors with increased stability and detection sensitivity for marine neurotoxins. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Biochemical and Electrophysiological Characterization of Two Sea Anemone Type 1 Potassium Toxins from a Geographically Distant Population of Bunodosoma caissarum
by Diego J. B. Orts, Steve Peigneur, Bruno Madio, Juliana S. Cassoli, Gabriela G. Montandon, Adriano M. C. Pimenta, José E. P. W. Bicudo, José C. Freitas, André J. Zaharenko and Jan Tytgat
Mar. Drugs 2013, 11(3), 655-679; https://doi.org/10.3390/md11030655 - 6 Mar 2013
Cited by 32 | Viewed by 9114
Abstract
Sea anemone (Cnidaria, Anthozoa) venom is an important source of bioactive compounds used as tools to study the pharmacology and structure-function of voltage-gated K+ channels (KV). These neurotoxins can be divided into four different types, according to their structure and [...] Read more.
Sea anemone (Cnidaria, Anthozoa) venom is an important source of bioactive compounds used as tools to study the pharmacology and structure-function of voltage-gated K+ channels (KV). These neurotoxins can be divided into four different types, according to their structure and mode of action. In this work, for the first time, two toxins were purified from the venom of Bunodosoma caissarum population from Saint Peter and Saint Paul Archipelago, Brazil. Sequence alignment and phylogenetic analysis reveals that BcsTx1 and BcsTx2 are the newest members of the sea anemone type 1 potassium channel toxins. Their functional characterization was performed by means of a wide electrophysiological screening on 12 different subtypes of KV channels (KV1.1–KV1.6; KV2.1; KV3.1; KV4.2; KV4.3; hERG and Shaker IR). BcsTx1 shows a high affinity for rKv1.2 over rKv1.6, hKv1.3, Shaker IR and rKv1.1, while Bcstx2 potently blocked rKv1.6 over hKv1.3, rKv1.1, Shaker IR and rKv1.2. Furthermore, we also report for the first time a venom composition and biological activity comparison between two geographically distant populations of sea anemones. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Article
Paralytic Toxins Accumulation and Tissue Expression of α-Amylase and Lipase Genes in the Pacific Oyster Crassostrea gigas Fed with the Neurotoxic Dinoflagellate Alexandrium catenella
by Jean-Luc Rolland, Kevin Pelletier, Estelle Masseret, Fabien Rieuvilleneuve, Veronique Savar, Adrien Santini, Zouher Amzil and Mohamed Laabir
Mar. Drugs 2012, 10(11), 2519-2534; https://doi.org/10.3390/md10112519 - 12 Nov 2012
Cited by 16 | Viewed by 7542
Abstract
The pacific oyster Crassostrea gigas was experimentally exposed to the neurotoxic Alexandrium catenella and a non-producer of PSTs, Alexandrium tamarense (control algae), at concentrations corresponding to those observed during the blooming period. At fixed time intervals, from 0 to 48 h, we determined [...] Read more.
The pacific oyster Crassostrea gigas was experimentally exposed to the neurotoxic Alexandrium catenella and a non-producer of PSTs, Alexandrium tamarense (control algae), at concentrations corresponding to those observed during the blooming period. At fixed time intervals, from 0 to 48 h, we determined the clearance rate, the total filtered cells, the composition of the fecal ribbons, the profile of the PSP toxins and the variation of the expression of two α-amylase and triacylglecerol lipase precursor (TLP) genes through semi-quantitative RT-PCR. The results showed a significant decrease of the clearance rate of C. gigas fed with both Alexandrium species. However, from 29 to 48 h, the clearance rate and cell filtration activity increased only in oysters fed with A. tamarense. The toxin concentrations in the digestive gland rose above the sanitary threshold in less than 48 h of exposure and GTX6, a compound absent in A. catenella cells, accumulated. The α-amylase B gene expression level increased significantly in the time interval from 6 to 48 h in the digestive gland of oysters fed with A. tamarense, whereas the TLP gene transcript was significantly up-regulated in the digestive gland of oysters fed with the neurotoxic A. catenella. All together, these results suggest that the digestion capacity could be affected by PSP toxins. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Review

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421 KiB  
Review
An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management
by Melissa A. Friedman, Mercedes Fernandez, Lorraine C. Backer, Robert W. Dickey, Jeffrey Bernstein, Kathleen Schrank, Steven Kibler, Wendy Stephan, Matthew O. Gribble, Paul Bienfang, Robert E. Bowen, Stacey Degrasse, Harold A. Flores Quintana, Christopher R. Loeffler, Richard Weisman, Donna Blythe, Elisa Berdalet, Ram Ayyar, Danielle Clarkson-Townsend, Karen Swajian, Ronald Benner, Tom Brewer and Lora E. Flemingadd Show full author list remove Hide full author list
Mar. Drugs 2017, 15(3), 72; https://doi.org/10.3390/md15030072 - 14 Mar 2017
Cited by 250 | Viewed by 25513
Abstract
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or [...] Read more.
Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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Review
Recent Trends in Marine Phycotoxins from Australian Coastal Waters
by Penelope Ajani, D. Tim Harwood and Shauna A. Murray
Mar. Drugs 2017, 15(2), 33; https://doi.org/10.3390/md15020033 - 9 Feb 2017
Cited by 44 | Viewed by 7336
Abstract
Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the marine food web, are of growing concern for Australia. These harmful algae pose a threat to ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest [...] Read more.
Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the marine food web, are of growing concern for Australia. These harmful algae pose a threat to ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest growing food sectors in the world. With better monitoring, advanced analytical skills and an increase in microalgal expertise, many phycotoxins have been identified in Australian coastal waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern, warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012 resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to improve toxin and organism detection methods, clarify the toxin profiles of species of phytoplankton and carry out both intra‐ and inter‐species toxicity comparisons. Future work also includes the application of rapid, real‐time molecular assays for the detection of harmful species and toxin genes. This information, in conjunction with a better understanding of the life histories and ecology of harmful bloom species, may lead to more appropriate management of environmental, health and economic resources. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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988 KiB  
Review
An Overview on the Marine Neurotoxin, Saxitoxin: Genetics, Molecular Targets, Methods of Detection and Ecological Functions
by Kathleen D. Cusick and Gary S. Sayler
Mar. Drugs 2013, 11(4), 991-1018; https://doi.org/10.3390/md11040991 - 27 Mar 2013
Cited by 236 | Viewed by 17496
Abstract
Marine neurotoxins are natural products produced by phytoplankton and select species of invertebrates and fish. These compounds interact with voltage-gated sodium, potassium and calcium channels and modulate the flux of these ions into various cell types. This review provides a summary of marine [...] Read more.
Marine neurotoxins are natural products produced by phytoplankton and select species of invertebrates and fish. These compounds interact with voltage-gated sodium, potassium and calcium channels and modulate the flux of these ions into various cell types. This review provides a summary of marine neurotoxins, including their structures, molecular targets and pharmacologies. Saxitoxin and its derivatives, collectively referred to as paralytic shellfish toxins (PSTs), are unique among neurotoxins in that they are found in both marine and freshwater environments by organisms inhabiting two kingdoms of life. Prokaryotic cyanobacteria are responsible for PST production in freshwater systems, while eukaryotic dinoflagellates are the main producers in marine waters. Bioaccumulation by filter-feeding bivalves and fish and subsequent transfer through the food web results in the potentially fatal human illnesses, paralytic shellfish poisoning and saxitoxin pufferfish poisoning. These illnesses are a result of saxitoxin’s ability to bind to the voltage-gated sodium channel, blocking the passage of nerve impulses and leading to death via respiratory paralysis. Recent advances in saxitoxin research are discussed, including the molecular biology of toxin synthesis, new protein targets, association with metal-binding motifs and methods of detection. The eco-evolutionary role(s) PSTs may serve for phytoplankton species that produce them are also discussed. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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904 KiB  
Review
Omega-Conotoxins as Experimental Tools and Therapeutics in Pain Management
by Heidi E. Hannon and William D. Atchison
Mar. Drugs 2013, 11(3), 680-699; https://doi.org/10.3390/md11030680 - 7 Mar 2013
Cited by 37 | Viewed by 11953
Abstract
Neuropathic pain afflicts a large percentage of the global population. This form of chronic, intractable pain arises when the peripheral or central nervous systems are damaged, either directly by lesion or indirectly through disease. The comorbidity of neuropathic pain with other diseases, including [...] Read more.
Neuropathic pain afflicts a large percentage of the global population. This form of chronic, intractable pain arises when the peripheral or central nervous systems are damaged, either directly by lesion or indirectly through disease. The comorbidity of neuropathic pain with other diseases, including diabetes, cancer, and AIDS, contributes to a complex pathogenesis and symptom profile. Because most patients present with neuropathic pain refractory to current first-line therapeutics, pharmaceuticals with greater efficacy in pain management are highly desired. In this review we discuss the growing application of ω-conotoxins, small peptides isolated from Conus species, in the management of neuropathic pain. These toxins are synthesized by predatory cone snails as a component of paralytic venoms. The potency and selectivity with which ω-conotoxins inhibit their molecular targets, voltage-gated Ca2+ channels, is advantageous in the treatment of neuropathic pain states, in which Ca2+ channel activity is characteristically aberrant. Although ω-conotoxins demonstrate analgesic efficacy in animal models of neuropathic pain and in human clinical trials, there remains a critical need to improve the convenience of peptide drug delivery methods, and reduce the number and severity of adverse effects associated with ω-conotoxin-based therapies. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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751 KiB  
Review
Jellyfish Stings and Their Management: A Review
by Luca Cegolon, William C. Heymann, John H. Lange and Giuseppe Mastrangelo
Mar. Drugs 2013, 11(2), 523-550; https://doi.org/10.3390/md11020523 - 22 Feb 2013
Cited by 158 | Viewed by 27878
Abstract
Jellyfish (cnidarians) have a worldwide distribution. Despite most being harmless, some species may cause local and also systemic reactions. Treatment of jellyfish envenomation is directed at: alleviating the local effects of venom, preventing further nematocyst discharges and controlling systemic reactions, including shock. In [...] Read more.
Jellyfish (cnidarians) have a worldwide distribution. Despite most being harmless, some species may cause local and also systemic reactions. Treatment of jellyfish envenomation is directed at: alleviating the local effects of venom, preventing further nematocyst discharges and controlling systemic reactions, including shock. In severe cases, the most important step is stabilizing and maintaining vital functions. With some differences between species, there seems to be evidence and consensus on oral/topical analgesics, hot water and ice packs as effective painkillers and on 30 s application of domestic vinegar (4%–6% acetic acid) to prevent further discharge of unfired nematocysts remaining on the skin. Conversely, alcohol, methylated spirits and fresh water should be carefully avoided, since they could massively discharge nematocysts; pressure immobilization bandaging should also be avoided, as laboratory studies show that it stimulates additional venom discharge from nematocysts. Most treatment approaches are presently founded on relatively weak evidence; therefore, further research (especially randomized clinical trials) is strongly recommended. Dissemination of appropriate treatment modalities should be deployed to better inform and educate those at risk. Adequate signage should be placed at beaches to notify tourists of the jellyfish risk. Swimmers in risky areas should wear protective equipment. Full article
(This article belongs to the Special Issue Marine Neurotoxins)
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