Search Results (107)

Domoic acid (DA) is a well-known seafood toxin produced by some species of marine phytoplankton in the genus Pseudo-nitzschia during harmful algal blooms (HABs). Acute toxic exposures induce overt clinical signs of neuroexcitotoxicity, such as seizures in mammals due to overstimulation of glutamate receptors in the central nervous system (CNS). Acute DA excitotoxicity via the CNS has been well-studied in both field poisoning events and laboratory exposure studies with rodent models, but little is known about the impacts of low-level DA exposures below those that cause outward signs of neurotoxicity; the impacts on other potential target organs, including the heart; or age-related sensitivities. Here, low-level DA exposures in young adult (9 mo) and old (24 mo) mice were conducted over multiple weeks. Mortality, cardiac function, frailty, and protein expression were quantified to assess age-related DA sensitivity and potential impacts on heart function. Echocardiography and proteome data confirm that chronic low-level DA exposure causes irreversible functional cardiomyopathy and protein remodeling in young adult mice that mimics natural cardiac aging. In addition, old mice exhibit higher mortality and frailty than young adult mice with the same low-level DA exposures. These results provide critical information for assessing potential health risks to humans who regularly consume seafood with low levels of DA. Full article

Human organoids and organ-on-chip/microphysiological systems (OoC/MPS) are increasingly used as new-approach methodologies for biotoxin assessment. They retain human-relevant tissue organization and enable interpretable analysis of exposure geometry, barrier transport, perfusion, and (when needed) multi-organ coupling. In this review, we synthesize primary evidence across major toxin classes, including bacterial enterotoxins (e.g., cholera toxin, heat-stable enterotoxins, Shiga toxins), mycotoxins (e.g., aflatoxin B1, ochratoxin A, deoxynivalenol), and algal/cyanobacterial toxins (e.g., saxitoxin, domoic acid, microcystins, biliatresone). We emphasize studies that clearly define toxin identity and exposure context and that demonstrate mechanism-critical model competencies under assay conditions. We highlight decision-informative functional endpoints that align with the dominant pathophysiology. These include cystic fibrosis transmembrane conductance regulator (CFTR)-dependent secretion in human enteroids/colonoids, transporter-linked proximal tubular injury in kidney MPS, gut–kidney axis injury from Shiga toxin-producing E. coli in microfluidic systems, and multi-electrode array (MEA) network readouts in human 3D neural tissues. We then summarize best practices that improve cross-study comparability. These include reporting delivered versus nominal exposure, assessing recovery/mass balance and device/material interactions, applying proportional biological qualification (polarity, transporter/enzymatic competence, functional stability), defining a minimal comparable endpoint core, and preserving QIVIVE readiness in reporting. Finally, we outline near-term priorities for the field, including chronic low-dose and mixture designs, harmonized reference panels and acceptance criteria, and fit-for-purpose escalation to coupled OoC/MPS only when perfusion or organ–organ coupling is expected to change the interpretation. Full article

In recent years, harmful algal blooms have led to frequent occurrences of shellfish toxin contamination, posing a significant threat to the safety of aquatic products and public health. As a potent neurotoxin, domoic acid (DA) can accumulate in shellfish, highlighting the urgent need for rapid and highly sensitive detection methods. In this study, we developed a fluorescent aptasensor based on a dual-signal amplification system by combining G-quadruplex (G4) dimers with multi-walled carbon nanotubes (CNTs). The sensor is designed with a hairpin-structured aptamer as the recognition probe, where short multi-walled CNTs serve as both a fluorescence quencher and platform, and G4 dimers are incorporated into the sensing interface to enhance signal output. In the absence of the target, the hairpin-structured aptamer remains closed, keeping the fluorescence signal “off”. Upon binding to DA, the aptamer undergoes a specific conformational change that exposes the G4-dimer sequence. The exposed sequence then binds to thioflavin T (ThT), which in turn generates a greatly enhanced fluorescence signal, leading to a substantial fluorescence enhancement and completing the second stage of the cascade amplification. Under optimal conditions, the constructed sensor achieves rapid detection of DA within 5 min, with a low detection limit of 1.1 ng/mL. This work presents a valuable tool for the rapid and sensitive detection of DA in shellfish, with promising applications in marine environmental monitoring and food safety regulation. Full article

Domoic acid (DA) is a neurotoxic terpenoid compound produced by certain marine algae. It accumulates through the food web and poses a significant threat to humans and animals by selectively targeting hippocampal neurons, leading to neuronal degeneration, necrosis, and subsequent memory impairment. The primary mechanism involves its potent agonism at glutamate receptors, which induces excessive calcium influx, resulting in excitotoxic cell swelling and death. Recent studies have further elucidated the critical role of downstream oxidative stress and other pathogenic factors in DA-induced neurotoxicity. These insights into its multifaceted mechanism have paved the way for novel therapeutic strategies, highlighting promising directions for future treatment development. Full article

Excitable neurons are intrinsically capable of firing action potentials (AP), yet a state of hyperexcitability is prevented in the central nervous system by powerful GABAergic inhibition. For this inhibition to be effective, it must occur before excitatory signals can initiate runaway activity, implying the existence of a proactive control system. To test for such proactive inhibition, we used Ca²⁺ imaging and patch-clamp recording to measure how hippocampal neurons respond to depolarization and glutamatergic agonists. In mature hippocampal cultures (14 days in vitro (DIV)) and acute brain slices from two-month-old rats, neurons exhibited non-simultaneous responses to various excitatory stimuli, including KCl, NH₄Cl, forskolin, domoic acid, and glutamate. We observed that the Ca²⁺ rise occurred significantly earlier in GABAergic neurons than in glutamatergic neurons. This delay in glutamatergic neurons was abolished by GABA(A) receptor inhibitors, suggesting a mechanism of preliminary γ-aminobutyric acid (GABA) release. We further found that these early-responding GABAergic neurons express calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs). Application of domoic acid induced an immediate Ca²⁺ increase in neurons expressing these receptors, but a delayed response in others. Crucially, when domoic acid was applied in the presence of the AMPA receptor inhibitors NBQX or GYKI-52466, the response delay in glutamatergic neurons was significantly prolonged. This confirms that CP-KARs on GABAergic neurons are responsible for the delayed excitation of glutamatergic neurons. In hippocampal slices from two-month-old rats, depolarization with 50 mM KCl revealed two distinct neuronal populations based on their calcium dynamics: a majority group (presumably glutamatergic) exhibited fluctuating Ca²⁺ signals, while a minority (presumably GABAergic) showed a steady, advancing increase in [Ca²⁺]i. This distinction was reinforced by the application of domoic acid. The “advancing-response” neurons reacted to domoic acid with a similar prompt increase, whereas the “fluctuating-response” neurons displayed an even more delayed and fluctuating reaction (80 s delay). Therefore, we identify a subgroup of hippocampal neurons—in both slices and cultures—that respond to depolarization and domoic acid with an early [Ca²⁺]_i signal. Consistent with our data from cultures, we conclude these early-responding neurons are GABAergic. Their early GABA release directly explains the delayed Ca²⁺ response observed in glutamatergic neurons. We propose that this proactive mechanism, mediated by CP-KARs on GABAergic neurons, is a primary means of protecting the network from hyperexcitation. Furthermore, the activity of these CP-KAR-expressing neurons is itself regulated by GABAergic neurons containing CP-AMPARs. Full article

Domoic acid (DA), produced by Pseudo-nitzschia diatoms, is the one of the major toxin threats from harmful algal blooms (HABs) on the west coast of the United States. DA events vary in magnitude, timing, and duration, and elucidating drivers for individual events is a persistent challenge. Monterey Bay experiences near-annual DA events and hosts long-term HAB monitoring at the Santa Cruz Municipal Wharf (SCW). Here we characterize two toxin events, occurring in May 2023 and March 2024. The events were similar in magnitude and duration, but an exploration of physical, biological, and chemical dynamics revealed distinct environmental drivers. These differences resulted in a significant deviation in cellular DA (cDA) within the same species of Pseudo-nitzschia. In addition, opportunistic solid-phase adsorption toxin tracking (SPATT) was used for environmental metabolomics. The novel application of SPATT revealed 159 metabolites that were strongly correlated with DA in both events and produced a spectral match to a new marine natural product using Global Natural Products Social Molecular Networking (GNPS). This work takes a multivariable approach to understanding toxin drivers and lends proof of concept for the integration of environmental metabolomics in HAB monitoring. Full article

Harmful algae are transported in various compartments of maritime vessels, making ports with heavy maritime traffic potential hotspots for their introduction and spread. In this study, we investigate the port of Papeete (Tahiti, French Polynesia), a key hub for numerous South Pacific shipping routes. Using metabarcoding on DNA extracted from water samples (environmental DNA, eDNA) we identified 21 species of harmful algae comprising to Bacillariophyceae (4), Dinophyceae (14), and Haptophyta (3 species). Three of those species are directly associated with fish mortality events without recognized toxigenic capacity. The remaining harmful algae species are known to produce a wide range of toxins, like the ciguatoxin produced by endemic Gambierdiscus sp., domoic acid, haemolysins, yessotoxins, and others. Health risks such as ciguatera and paralytic shellfish poisoning were identified. An increase in Gambierdiscus frequency in Papeete port waters was parallel to an increase in ciguatera fish poisoning events in Tahiti, which suggests the value of eDNA analysis for early warning of harmful algae presence. Management measures, including banning fishing near the ports, could prevent public health risks associated with harmful algae blooms. Full article

Domoic acid (DA) is a potent neurotoxin that poses public health concerns, especially for children and adolescents during critical neurodevelopmental periods. In the present study, urinary DA concentrations in 216 children and adolescents at the age of 6 to 18 in southern China were determined using a novel dansyl-chloride (DNS-Cl) derivatization high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method with ultrahigh sensitivity (LOQ: 0.087 ng/mL). The median urinary DA concentration was 2.17 ng/mL (interquartile range (IQR): 0.87–4.08 ng/mL). When analyzed by age group, the medians were 1.40 ng/mL (6–9 years; IQR: 0.55–3.49 ng/mL), 2.16 ng/mL (10–13 years; IQR: 0.94–4.07 ng/mL), and 2.93 ng/mL (14–18 years; IQR: 1.06–5.06 ng/mL). Our findings revealed that urinary DA concentrations increased with age and varied significantly across different body mass index groups (p < 0.05), while no significant gender differences were observed. The estimated daily intake (1.73–374 ng/kg/day) remained below established safety thresholds. This study represents the first systematic biomonitoring of urinary DA exposure in children and adolescents from southern China’s coastal communities, addressing critical knowledge gaps and establishing baseline data amid rising harmful algal bloom frequency. Full article

The marine diatoms Pseudo-nitzschia spp. are globally distributed primary producers, with certain species capable of producing neurotoxin domoic acid (DA), causing amnesic shellfish poisoning (ASP). This study investigates the toxicity and growth rates of Pseudo-nitzschia species isolated from aquaculture areas in the Central Adriatic Sea. A total of 54 strains from eight species were analysed, with strains originating from four different study sites. Growth rates and toxin production were examined across different growth phases in other species and strains. Most species, including P. allochrona, P. calliantha, P. delicatissima, P. fraudulenta, P. galaxiae, P. mannii, and P. multistriata, did not produce DA at any growth phase. The only species that showed toxin production, at 18 °C was P. pseudodelicatissima (0.0007–0.0250 pg cell⁻¹). Notably, the majority of P. pseudodelicatissima strains were toxic in the decay phase and some strains showed continuous toxin production throughout all growth phases. The highest growth rates for the analysed species were recorded in strains of P. delicatissima, which also exhibited the highest cell abundance (8.19 × 10⁵ cell mL⁻¹), followed by the species P. allochrona, P. mannii and P. pseudodelicatissima. Full article

Cyanobacterial harmful blooms (CyanoHABs) in lakes, estuaries, and freshwater reser-voirs represent a significant risk to water authorities worldwide due to their cyanotoxins and economic impacts. The duration, spread, and severity of CyanoHABs have markedly increased over the past decades. The article addresses CyanoHABs, cyanotoxins, and monitoring methodologies in post-Soviet and Central Asian countries. This particular region was selected for the systematic review due to its relative lack of representation in global CyanoHABs reporting, particularly in Central Asia. The main aim of this systematic review was to analyze the primary literature available from 2010–2024 to examine the current situation of CyanoHAB detection, monitoring, and management in Central Asia and post-Soviet countries. Following a detailed database search in several selected data-bases (Google Scholar, Pubmed, Web of Science (WOS), Scopus, Elibrary, ENU, and KazNU) along with additional hand searching and citation searching, 121 primary articles reporting 214 local cyanobacterial bloom cases were selected for this review. Aquatic cyanotoxins were reported in water bodies of eight countries, including high concentrations of microcystins that often exceeded reference values established by the World Health Organization (WHO). Advancing monitoring efforts in Baltic countries, Belarus, and the Russian Federation differed from only a few Central Asian reports. However, Central Asian aquatic ecosystems are especially threatened by rising anthropogenic pressures (i.e., water use, intensive agriculture, and pollution), climate change, and the lack of adequate ecological surveillance. We hypothesize that recent Caspian seal mass mortality events have been caused by a combination of infection (viral or bacterial) and exposure to algal neurotoxins resulting from harmful algal blooms of Pseudo-nitzschia. We conclude that there is an urgent need to improve the assessment of cyanobacterial blooms in Central Asia and post-Soviet countries. Full article

Phytoplankton are single-celled microorganisms with short generation times that may comprise high diversity in genetic and phenotypic traits, allowing them to acclimate to changes rapidly. High intraspecific genetic variation is well known in phytoplankton, but less is known about variation in physiological traits. To investigate variability and plasticity in genetic, morphological, and physiological traits of the toxigenic diatom genus Pseudo-nitzschia in a global warming scenario, we exposed 40 strains of the cold-water P. seriata to different temperatures (2 °C, 6 °C and 10 °C). The maximum growth rate and cellular toxin content showed extensive intraspecific variation, whereas morphological and genetic variation was minor. Thermal reaction norms showed a general increase in growth rate with increasing temperature; however, three distinct types of thermal responses were found among the 40 strains. All 40 strains contained toxins (domoic acid) in both exponential and stationary growth phase, and toxin content increased significantly with temperature. Most strains (>87%) contained measurable levels of domoic acid at all three temperatures. In conclusion, P. seriata shows extensive intraspecific variation in measured physiological traits like growth and toxin content, a variation exceeding the response of each strain to increases in temperature. Intraspecific variation in harmful species thus needs attention for the future understanding of food web dynamics, as well as the management and forecasting of harmful blooms. Full article

As oceans warm, harmful algal blooms (HABs) are expected to increase, including blooms of Pseudo-nitzschia, a diatom that produces domoic acid (DA), which is a potent neurotoxin. Regulatory limits for human consumption (0.075–0.1 mg/kg/day; acute exposure) exist for the Pacific razor clam; however, fisheries currently do not have regulatory limits for chronic low-level exposure to DA even though razor clams can retain DA for over a year after an algal bloom. For bivalves, exposure to marine toxins may disrupt important cellular processes, leading to concerns about effects on their overall health and potential population- and ecosystem-level impacts. Transcriptomics was used to identify differentially expressed genes in razor clams (N = 30) from Long Beach, WA, collected prior to, during, and after a DA-producing bloom. Differentially expressed genes were identified that may indicate exposure of razor clams to DA, including clams with tissue DA concentrations that fall below regulatory limits for human consumption. Targeting these genes in real-time PCR assays may provide an early warning system for routine monitoring of DA in clams. Our results suggest DA exposure is associated with physiological responses ranging from decreased immune function to the potential disruption of cell communication, including retinoic acid catabolic processes, cell adhesion, collagen fibril organization, and immune effector processes. This work may also allow us to examine potential drivers of population-level change and whether chronic lower-level exposure to DA negatively impacts razor clam function, consequently affecting individual and population health. Full article

Paretic and paralyzing syndromes affecting wild birds are widely described in the literature, with outbreaks showing an increase in frequency and intensity worldwide during recent years. In the Iberian Peninsula, a paretic clinical picture without known etiology affecting mostly gulls has been reported during the last few decades. This paretic syndrome (PS) affects waterbirds and is characterized by a set of signs of ascendent flaccid paralysis, dyspnea, and diarrhea at different levels of severity. This study presents the first macro-analysis of some potential etiological PS agents in wild birds in southern Portugal. Other possible etiologies of PS related to nutritional deficiencies and environmental pollutants were not studied but are also discussed here. A total of 571 samples, belonging to 377 individuals with (n = 336) and without (n = 41) PS signs, have been tested for seven different toxins groups (botulinum neurotoxin (BoNT), paralytic shellfish toxins (PSTs), domoic acid (DA), anatoxin-a (ATX-a), cylindrospermopsin (CYN), tetrodotoxins (TTXs), and microcystins (MCs)) and three viral infections (gull adenovirus (GA), Newcastle disease virus (NVD), and highly pathogenic avian influenza viruses (HPAIV)). Of all the birds tested for botulinum neurotoxin, those with PS signs were positive (100%) and those without PS signs were negative (0%), confirming an association between PS and botulism. Some samples were positive for PSTs and MCs, but the prevalence in birds with PS signs was not significantly higher (2.5% and 5.3%, respectively) than in birds without signs (5.4% and 5.4%, respectively). Two birds without PS signs were positive for highly pathogenic avian influenza virus. The presence of the rest of the toxins and viruses was negative for all the samples tested. Our results support the relevant contribution of botulinum neurotoxin in the PS outbreaks observed in several species of aquatic birds in the last decades in southern Portugal, suggesting it could be one of the main causes of mortality in waterbirds. Full article

Biotoxins produced by harmful algal blooms (HABs) are a substantial global threat to ocean and human health. Domoic acid (DA) is one such biotoxin whose negative impacts are forecasted to increase with climate change and coastal development. This manuscript serves as a review of DA toxicosis after environmental exposure in humans and wildlife, including an introduction to HAB toxins, the history of DA toxicosis, DA production, toxicokinetic properties of DA, susceptibility, clinical signs, DA detection methods and other diagnostic tests, time course of toxicosis, treatment, prognostics, and recommendations for future research. Additionally, we highlight the utility of California sea lions (CSLs; Zalophus californianus) as a model and sentinel of environmental DA exposure. Full article

The marine diatom genus Pseudo-nitzschia comprises cosmopolitan phytoplankton species commonly present in the Adriatic Sea. Species within the genus Pseudo-nitzschia have been of significant concern because they produce domoic acid (DA), which can cause amnesic shellfish poisoning (ASP). In this study, we identified Pseudo-nitzschia species along the Central and Southeastern Adriatic Sea, where monthly sampling carried out from February 2022 to February 2024 allowed for comprehensive species documentation. Pseudo-nitzschia species cell cultures isolated from the study areas were morphologically and molecularly analysed. Morphological analyses were performed using a scanning electron microscope (FE-SEM/STEM), while molecular analyses were conducted, targeting the ITS1-5.8S-ITS2, LSU, and rbcL regions, to confirm species identity. This integrative approach led to the identification of eight species: Pseudo-nitzschia allochrona, Pseudo-nitzschia calliantha, Pseudo-nitzschia delicatissima, Pseudo-nitzschia fraudulenta, Pseudo-nitzschia mannii, Pseudo-nitzschia multistriata, Pseudo-nitzschia pseudodelicatissima, and Pseudo-nitzschia subfraudulenta. Our findings underscore the value of a combined approach for reliable species identification and contribute to the development of genetic sequence databases that support the advancement of next-generation methods such as metabarcoding. This research emphasises the importance of combined morphological and molecular methods for the differentiation of the cryptic and pseudo-cryptic Pseudo-nitzschia species. Full article