RESUMEN
The excitatory neurotoxin domoic acid (DA) consistently contaminates food webs in coastal regions around the world. Acute exposure to the toxin causes Amnesic Shellfish Poisoning, a potentially lethal syndrome of gastrointestinal- and seizure-related outcomes. Both advanced age and male sex have been suggested to contribute to interindividual DA susceptibility. To test this, we administered DA doses between 0.5 and 2.5 mg/kg body weight to female and male C57Bl/6 mice at adult (7-9-month-old) and aged (25-28-month-old) life stages and observed seizure-related activity for 90 min, at which point we euthanized the mice and collected serum, cortical, and kidney samples. We observed severe clonic-tonic convulsions in some aged individuals, but not in younger adults. We also saw an association between advanced age and the incidence of a moderately severe seizure-related outcome, hindlimb tremors, and between advanced age and overall symptom severity and persistence. Surprisingly, we additionally report that female mice, particularly aged female mice, demonstrated more severe neurotoxic symptoms following acute exposure to DA than males. Both age and sex patterns were reflected in tissue DA concentrations as well: aged mice and females had generally higher concentrations of DA in their tissues at 90 min post-exposure. This study contributes to the body of work that can inform intelligent, evidence-based public health protections for communities threatened by more frequent and extensive DA-producing algal blooms.
Asunto(s)
Ácido Kaínico , Neurotoxinas , Masculino , Femenino , Animales , Ratones , Ácido Kaínico/toxicidad , Neurotoxinas/toxicidad , Toxinas Marinas/toxicidad , Convulsiones/inducido químicamente , Modelos Animales de EnfermedadRESUMEN
Domoic acid (DA) is a naturally produced neurotoxin synthesized by marine diatoms in the genus Pseudo-nitzschia. DA accumulates in filter-feeders such as shellfish, and can cause severe neurotoxicity when contaminated seafood is ingested, resulting in Amnesic Shellfish Poisoning (ASP) in humans. Overt clinical signs of neurotoxicity include seizures and disorientation. ASP is a significant public health concern, and though seafood regulations have effectively minimized the human risk of severe acute DA poisoning, the effects of exposure at asymptomatic levels are poorly understood. The objective of this study was to determine the effects of exposure to symptomatic and asymptomatic doses of DA on gene expression patterns in the zebrafish brain. We exposed adult zebrafish to either a symptomatic (1.1 ± 0.2 µg DA/g fish) or an asymptomatic (0.31 ± 0.03 µg DA/g fish) dose of DA by intracelomic injection and sampled at 24, 48 and 168 h post-injection. Transcriptional profiling was done using Agilent and Affymetrix microarrays. Our analysis revealed distinct, non-overlapping changes in gene expression between the two doses. We found that the majority of transcriptional changes were observed at 24 h post-injection with both doses. Interestingly, asymptomatic exposure produced more persistent transcriptional effects - in response to symptomatic dose exposure, we observed only one differentially expressed gene one week after exposure, compared to 26 in the asymptomatic dose at the same time (FDR <0.05). GO term analysis revealed that symptomatic DA exposure affected genes associated with peptidyl proline modification and retinoic acid metabolism. Asymptomatic exposure caused differential expression of genes that were associated with GO terms including circadian rhythms and visual system, and also the neuroactive ligand-receptor signaling KEGG pathway. Overall, these results suggest that transcriptional responses are specific to the DA dose and that asymptomatic exposure can cause long-term changes. Further studies are needed to characterize the potential downstream neurobehavioral impacts of DA exposure.
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Diatomeas , Contaminantes Químicos del Agua , Animales , Humanos , Pez Cebra/genética , Neurotoxinas/toxicidad , Ligandos , Contaminantes Químicos del Agua/toxicidad , Ácido Kaínico/toxicidad , Encéfalo , Diatomeas/genética , Expresión Génica , Tretinoina/farmacología , ProlinaRESUMEN
In recent decades, harmful algal blooms (HABs) producing paralytic shellfish toxins (including saxitoxin, STX) have become increasingly frequent in the marine waters of Alaska, USA, subjecting Pacific Arctic and subarctic communities and wildlife to increased toxin exposure risks. Research on the risks of HAB toxin exposures to marine mammal health commonly relies on the sampling of marine mammal gastrointestinal (GI) contents to quantify HAB toxins, yet no studies have been published testing the stability of STX in marine mammal GI matrices. An understanding of STX stability in test matrices under storage and handling conditions is imperative to the integrity of toxin quantifications and conclusions drawn thereby. Here, STX stability is characterized in field-collected bowhead whale feces (stored raw in several treatments) and in fecal extracts (50% methanol, MeOH) over multiple time points. Toxin stability, as the percent of initial concentration (T0), was reported for each storage treatment and time point. STX was stable (mean 99% T0) in 50% MeOH extracts over the 8-week study period, and there was no significant difference in STX concentrations quantified in split fecal samples extracted in 80% ethanol (EtOH) and 50% MeOH. STX was also relatively stable in raw fecal material stored in the freezer (mean 94% T0) and the refrigerator (mean 93% T0) up to 8 weeks. STX degraded over time in the room-temperature dark, room-temperature light, and warm treatments to means of 48 ± 1.9, 38 ± 2.8, and 20 ± 0.7% T0, respectively, after 8 weeks (mean ± standard error; SE). Additional opportunistically analyzed samples frozen for ≤4.5 years also showed STX to be relatively stable (mean 97% T0). Mean percent of T0 was measured slightly above 100% in some extracts following some treatments, and (most notably) at some long-term frozen time points, likely due to evaporation from samples causing STX to concentrate, or variability between ELISA plates. Overall, these results suggest that long-term frozen storage of raw fecal samples and the analysis of extracts within 8 weeks of extraction in 50% MeOH is sufficient for obtaining accurate STX quantifications in marine mammal fecal material without concerns about significant degradation.
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Ballena de Groenlandia , Saxitoxina , Animales , Etanol , Heces/química , Metanol , Saxitoxina/análisisRESUMEN
Climate change-related ocean warming and reduction in Arctic sea ice extent, duration and thickness increase the risk of toxic blooms of the dinoflagellate Alexandrium catenella in the Alaskan Arctic. This algal species produces neurotoxins that impact marine wildlife health and cause the human illness known as paralytic shellfish poisoning (PSP). This study reports Paralytic Shellfish Toxin (PST) concentrations quantified in Arctic food web samples that include phytoplankton, zooplankton, benthic clams, benthic worms, and pelagic fish collected throughout summer 2019 during anomalously warm ocean conditions. PSTs (saxitoxin equivalents, STX eq.) were detected in all trophic levels with concentrations above the seafood safety regulatory limit (80 µg STX eq. 100 g-1) in benthic clams collected offshore on the continental shelf in the Beaufort, Chukchi, and Bering Seas. Most notably, toxic benthic clams (Macoma calcarea) were found north of Saint Lawrence Island where Pacific walruses (Odobenus rosmarus) are known to forage for a variety of benthic species, including Macoma. Additionally, fecal samples collected from 13 walruses harvested for subsistence purposes near Saint Lawrence Island during March to May 2019, all contained detectable levels of STX, with fecal samples from two animals (78 and 72 µg STX eq. 100 g-1) near the seafood safety regulatory limit. In contrast, 64% of fecal samples from zooplankton-feeding bowhead whales (n = 9) harvested between March and September 2019 in coastal waters of the Beaufort Sea near Utqiagvik (formerly Barrow) and Kaktovik were toxin-positive, and those levels were significantly lower than in walruses (max bowhead 8.5 µg STX eq. 100 g-1). This was consistent with the lower concentrations of PSTs found in regional zooplankton prey. Maximum ecologically-relevant daily toxin doses to walruses feeding on clams and bowhead whales feeding on zooplankton were estimated to be 21.5 and 0.7 µg STX eq. kg body weight-1 day-1, respectively, suggesting that walruses had higher PST exposures than bowhead whales. Average and maximum STX doses in walruses were in the range reported previously to cause illness and/or death in humans and humpback whales, while bowhead whale doses were well below those levels. These findings raise concerns regarding potential increases in PST/STX exposure risks and health impacts to Arctic marine mammals as ocean warming and sea ice reduction continue.
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Bivalvos , Ballena de Groenlandia , Dinoflagelados , Animales , Cadena Alimentaria , Océanos y Mares , Saxitoxina , Mariscos , Morsas , ZooplanctonRESUMEN
Among the organisms that spread into and flourish in Arctic waters with rising temperatures and sea ice loss are toxic algae, a group of harmful algal bloom species that produce potent biotoxins. Alexandrium catenella, a cyst-forming dinoflagellate that causes paralytic shellfish poisoning worldwide, has been a significant threat to human health in southeastern Alaska for centuries. It is known to be transported into Arctic regions in waters transiting northward through the Bering Strait, yet there is little recognition of this organism as a human health concern north of the Strait. Here, we describe an exceptionally large A. catenella benthic cyst bed and hydrographic conditions across the Chukchi Sea that support germination and development of recurrent, locally originating and self-seeding blooms. Two prominent cyst accumulation zones result from deposition promoted by weak circulation. Cyst concentrations are among the highest reported globally for this species, and the cyst bed is at least 6× larger in area than any other. These extraordinary accumulations are attributed to repeated inputs from advected southern blooms and to localized cyst formation and deposition. Over the past two decades, warming has likely increased the magnitude of the germination flux twofold and advanced the timing of cell inoculation into the euphotic zone by 20 d. Conditions are also now favorable for bloom development in surface waters. The region is poised to support annually recurrent A. catenella blooms that are massive in scale, posing a significant and worrisome threat to public and ecosystem health in Alaskan Arctic communities where economies are subsistence based.
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Dinoflagelados/crecimiento & desarrollo , Dinoflagelados/metabolismo , Floraciones de Algas Nocivas/fisiología , Neurotoxinas/metabolismo , Intoxicación por Mariscos , Alaska , Regiones Árticas , Cambio Climático , Ecosistema , Sedimentos Geológicos/parasitología , Calor , Humanos , Cubierta de Hielo , Salud PúblicaRESUMEN
Domoic acid (DA) and saxitoxin (STX)-producing algae are present in Alaskan seas, presenting exposure risks to marine mammals that may be increasing due to climate change. To investigate potential increases in exposure risks to four pagophilic ice seal species (Erignathus barbatus, bearded seals; Pusa hispida, ringed seals; Phoca largha, spotted seals; and Histriophoca fasciata, ribbon seals), this study analyzed samples from 998 seals harvested for subsistence purposes in western and northern Alaska during 2005-2019 for DA and STX. Both toxins were detected in bearded, ringed, and spotted seals, though no clinical signs of acute neurotoxicity were reported in harvested seals. Bearded seals had the highest prevalence of each toxin, followed by ringed seals. Bearded seal stomach content samples from the Bering Sea showed a significant increase in DA prevalence with time (logistic regression, p = .004). These findings are consistent with predicted northward expansion of DA-producing algae. A comparison of paired samples taken from the stomachs and colons of 15 seals found that colon content consistently had higher concentrations of both toxins. Collectively, these results suggest that ice seals, particularly bearded seals (benthic foraging specialists), are suitable sentinels for monitoring HAB prevalence in the Pacific Arctic and subarctic.
RESUMEN
Domoic acid (DA), the toxin causing amnesic shellfish poisoning (ASP), is produced globally by some diatoms in the genus Pseudo-nitzschia. DA has been detected in several marine mammal species in the Alaskan Arctic, raising health concerns for marine mammals and subsistence communities dependent upon them. Gastrointestinal matrices are routinely used to detect Harmful Algal Bloom (HAB) toxin presence in marine mammals, yet DA stability has only been studied extensively in shellfish-related matrices. To address this knowledge gap, we quantified DA in bowhead whale fecal samples at multiple time points for two groups: (1) 50% methanol extracts from feces, and (2) raw feces stored in several conditions. DA concentrations decreased to 70 ± 7.1% of time zero (T0) in the 50% methanol extracts after 2 weeks, but remained steady until the final time point at 5 weeks (66 ± 5.7% T0). In contrast, DA concentrations were stable or increased in raw fecal material after 8 weeks of freezer storage (-20 °C), at room temperature (RT) in the dark, or refrigerated at 1 °C. DA concentrations in raw feces stored in an incubator (37 °C) or at RT in the light decreased to 77 ± 2.8% and 90 ± 15.0% T0 at 8 weeks, respectively. Evaporation during storage of raw fecal material is a likely cause of the increased DA concentrations observed over time with the highest increase to 126 ± 7.6% T0 after 3.2 years of frozen storage. These results provide valuable information for developing appropriate sample storage procedures for marine mammal fecal samples.
Asunto(s)
Ballena de Groenlandia , Heces/química , Ácido Kaínico/análogos & derivados , Toxinas Marinas/química , Animales , Ácido Kaínico/químicaRESUMEN
As harmful algal blooms (HABs) increase in magnitude and duration worldwide, they are becoming an expanding threat to marine wildlife. Over the past decade, blooms of algae that produce the neurotoxins domoic acid (DA) and saxitoxin (STX) and documented concurrent seabird mortality events have increased bicoastally in the United States. We conducted a retrospective analysis of HAB related mortality events in California, Washington, and Rhode Island between 2007 and 2018 involving 12 species of seabirds, to document the levels, ranges, and patterns of DA and STX in eight sample types (kidney, liver, stomach, intestinal, cloacal, cecal contents, bile, blood) collected from birds during these events. Samples (n = 182) from 83 birds were examined for DA (n = 135) or STX (n = 17) or both toxins simultaneously (n = 30), using ELISA or LCMS at the National Oceanographic and Atmospheric Administration, National Marine Fisheries Service (NOAA-NMFS) Wildlife Algal-toxin Research and Response Network (WARRN-West) or the University of California, Santa Cruz (UCSC). DA or STX was detected in seven of the sample types with STX below the minimum detection limit in blood for the three samples tested. DA was found in 70% and STX was found in 23% of all tested samples. The ranges of detectable levels of DA and STX in all samples were 0.65-681,190.00 ng g-1 and 2.00-20.95 ng g-1, respectively. Cloacal contents from a Pacific loon (Gavia pacifica) collected in 2017 from Ventura County, California, had the highest maximum level of DA for all samples and species tested in this study. The highest level of STX for all samples and species was detected in the bile of a northern fulmar (Fulmarus glacialis) collected in 2018 from San Luis Obispo County, California. DA detections were consistently found in gastrointestinal samples, liver, bile, and kidney, whereas STX detections were most frequently seen in liver and bile samples. Co-occurring HAB toxins (DA and STX) were detected in white-winged scoters (Melanitta deglandi) in 2009, a Brandt's cormorant (Phalacrocorax penicillatus) in 2015, and a northern fulmar and common murre (Uria aalge) in 2018. This article provides DA and STX tissue concentrations and patterns in avian samples and shows the utility of various sample types for the detection of HAB toxins. Future research to understand the pharmacodynamics of these toxins in avian species and to establish lethal doses in various bird species would be beneficial.
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Aves , Saxitoxina , Animales , Ácido Kaínico/análogos & derivados , Estudios Retrospectivos , Rhode Island , Estados Unidos , WashingtónRESUMEN
Published baseline data on biotoxin exposure in cetaceans is sparse but critical for interpreting mortality events as harmful algal blooms increase in frequency and duration. We present the first synthesis of domoic acid (DA), saxitoxin (STX), okadaic acid (OA), and microcystin detections in the feces and urine of stranded and bycaught southern California cetaceans, over an 18 year period (2001-2018), along with corresponding stomach content data. DA was detected in 13 out of 19 cetacean species, most often in harbor porpoise (Phocoena phocoena) (81.8%, n = 22) and long-beaked common dolphins (Delphinus delphis bairdii) (74%, n = 231). Maximum DA concentrations of 324,000 ng/g in feces and 271, 967 ng/ml in urine were observed in D. d. bairdii. DA was detected more frequently and at higher concentrations in male vs. female D. d. bairdii. Higher fecal DA concentrations in D. d. bairdii were associated with a greater proportion of northern anchovy (Engraulis mordax) in the diet, indicating it may be a primary vector of DA. Fecal DA concentrations for D. d. bairdii off Point Conception were greater than those from animals sampled off Los Angeles and San Diego counties, reflecting greater primary productivity and higher Pseudo-nitzschia spp. abundance in that region and a greater abundance of E. mordax in the diet. STX was detected at low levels (fecal max = 7.5 ng/g, urine max = 17 ng/ml) in 3.6% (n = 165) of individuals from 3 out of 11 species. The occurrence of E. mordax in 100% of the 3 examined stomachs suggests this species could be a primary vector of the detected STX. OA was detected in 2.4% of tested individuals (n = 85) at a maximum fecal concentration of 422.8 ng/g. Microcystin was detected in 14.3% (n = 7) of tested individuals with a maximum liver concentration of 96.8 ppb.
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Monitoreo del Ambiente , Saxitoxina , Animales , California , Cetáceos , Floraciones de Algas Nocivas , Saxitoxina/análisisRESUMEN
Domoic acid (DA), the causative agent for the human syndrome Amnesic Shellfish Poisoning (ASP), is a potent, naturally occurring neurotoxin produced by common marine algae. DA accumulates in seafood, and humans and wildlife alike can subsequently be exposed when consuming DA-contaminated shellfish or finfish. While strong regulatory limits protect people from the acute effects associated with ASP, DA is an increasingly significant public health concern, particularly for coastal dwelling populations, and there is a growing body of evidence suggesting that there are significant health consequences following repeated exposures to levels of the toxin below current safety guidelines. However, gaps in scientific knowledge make it difficult to precisely determine the risks of contemporary low-level exposure scenarios. The present review characterizes the toxicokinetics and neurotoxicology of DA, discussing results from clinical and preclinical studies after both adult and developmental DA exposure. The review also highlights crucial areas for future DA research and makes the case that DA safety limits need to be reassessed to best protect public health from deleterious effects of this widespread marine toxin.
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Exposición a Riesgos Ambientales , Ácido Kaínico/análogos & derivados , Salud Pública , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Humanos , Ácido Kaínico/efectos adversos , Medición de RiesgoRESUMEN
Harmful algal blooms (HABs) are diverse phenomena involving multiple. species and classes of algae that occupy a broad range of habitats from lakes to oceans and produce a multiplicity of toxins or bioactive compounds that impact many different resources. Here, a review of the status of this complex array of marine HAB problems in the U.S. is presented, providing historical information and trends as well as future perspectives. The study relies on thirty years (1990-2019) of data in HAEDAT - the IOC-ICES-PICES Harmful Algal Event database, but also includes many other reports. At a qualitative level, the U.S. national HAB problem is far more extensive than was the case decades ago, with more toxic species and toxins to monitor, as well as a larger range of impacted resources and areas affected. Quantitatively, no significant trend is seen for paralytic shellfish toxin (PST) events over the study interval, though there is clear evidence of the expansion of the problem into new regions and the emergence of a species that produces PSTs in Florida - Pyrodinium bahamense. Amnesic shellfish toxin (AST) events have significantly increased in the U.S., with an overall pattern of frequent outbreaks on the West Coast, emerging, recurring outbreaks on the East Coast, and sporadic incidents in the Gulf of Mexico. Despite the long historical record of neurotoxic shellfish toxin (NST) events, no significant trend is observed over the past 30 years. The recent emergence of diarrhetic shellfish toxins (DSTs) in the U.S. began along the Gulf Coast in 2008 and expanded to the West and East Coasts, though no significant trend through time is seen since then. Ciguatoxin (CTX) events caused by Gambierdiscus dinoflagellates have long impacted tropical and subtropical locations in the U.S., but due to a lack of monitoring programs as well as under-reporting of illnesses, data on these events are not available for time series analysis. Geographic expansion of Gambierdiscus into temperate and non-endemic areas (e.g., northern Gulf of Mexico) is apparent, and fostered by ocean warming. HAB-related marine wildlife morbidity and mortality events appear to be increasing, with statistically significant increasing trends observed in marine mammal poisonings caused by ASTs along the coast of California and NSTs in Florida. Since their first occurrence in 1985 in New York, brown tides resulting from high-density blooms of Aureococcus have spread south to Delaware, Maryland, and Virginia, while those caused by Aureoumbra have spread from the Gulf Coast to the east coast of Florida. Blooms of Margalefidinium polykrikoides occurred in four locations in the U.S. from 1921-2001 but have appeared in more than 15 â¯U.S. estuaries since then, with ocean warming implicated as a causative factor. Numerous blooms of toxic cyanobacteria have been documented in all 50 â¯U.S. states and the transport of cyanotoxins from freshwater systems into marine coastal waters is a recently identified and potentially significant threat to public and ecosystem health. Taken together, there is a significant increasing trend in all HAB events in HAEDAT over the 30-year study interval. Part of this observed HAB expansion simply reflects a better realization of the true or historic scale of the problem, long obscured by inadequate monitoring. Other contributing factors include the dispersion of species to new areas, the discovery of new HAB poisoning syndromes or impacts, and the stimulatory effects of human activities like nutrient pollution, aquaculture expansion, and ocean warming, among others. One result of this multifaceted expansion is that many regions of the U.S. now face a daunting diversity of species and toxins, representing a significant and growing challenge to resource managers and public health officials in terms of toxins, regions, and time intervals to monitor, and necessitating new approaches to monitoring and management. Mobilization of funding and resources for research, monitoring and management of HABs requires accurate information on the scale and nature of the national problem. HAEDAT and other databases can be of great value in this regard but efforts are needed to expand and sustain the collection of data regionally and nationally.
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Ecosistema , Floraciones de Algas Nocivas , Animales , Florida , Golfo de México , Océanos y Mares , Estados Unidos , VirginiaRESUMEN
BACKGROUND: The vaquita of Mexico is critically endangered, with a population less than 19 individuals in 2018. The population continues to decline and gillnet use continues in vaquita habitat. METHODS: Nine vaquita carcases were examined from 2016 to 2018 to establish cause of death. Concentrations of polychlorinated biphenyls (PCBs), DDTs and polybrominated diphenyl ethers (PBDEs) in blubber (n=3) were determined using gas chromatography/mass spectrometry and faeces tested for domoic acid and saxitoxin. RESULTS: Carcases were in good nutritional status and had lesions and full stomachs consistent with fisheries bycatch. PCB, DDT and PBDE concentrations ranged between 94 and 180 ng/g, 500 and 1200 ng/g and 97 and 210 ng/g lipid weight, respectively, which are low compared with other marine mammals. No saxitoxin or domoic acid was detected. CONCLUSION: These findings support the conclusion that bycatch is the primary source of vaquita population decline and emphasise the need for stronger measures to eliminate gillnets from the Upper Gulf of California, Mexico.
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Conservación de los Recursos Naturales , Phocoena , Animales , California , Explotaciones Pesqueras , México , Contaminantes del Agua/análisisRESUMEN
Mass mortality events are increasing in frequency and magnitude, potentially linked with ongoing climate change. In October 2016 through January 2017, St. Paul Island, Bering Sea, Alaska, experienced a mortality event of alcids (family: Alcidae), with over 350 carcasses recovered. Almost three-quarters of the carcasses were unscavenged, a rate much higher than in baseline surveys (17%), suggesting ongoing deposition and elevated mortality around St Paul over a 2-3 month period. Based on the observation that carcasses were not observed on the neighboring island of St. George, we bounded the at-sea distribution of moribund birds, and estimated all species mortality at 3,150 to 8,800 birds. The event was particularly anomalous given the late fall/winter timing when low numbers of beached birds are typical. In addition, the predominance of Tufted puffins (Fratercula cirrhata, 79% of carcass finds) and Crested auklets (Aethia cristatella, 11% of carcass finds) was unusual, as these species are nearly absent from long-term baseline surveys. Collected specimens were severely emaciated, suggesting starvation as the ultimate cause of mortality. The majority (95%, N = 245) of Tufted puffins were adults regrowing flight feathers, indicating a potential contribution of molt stress. Immediately prior to this event, shifts in zooplankton community composition and in forage fish distribution and energy density were documented in the eastern Bering Sea following a period of elevated sea surface temperatures, evidence cumulatively suggestive of a bottom-up shift in seabird prey availability. We posit that shifts in prey composition and/or distribution, combined with the onset of molt, resulted in this mortality event.
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Causas de Muerte , Charadriiformes/fisiología , Distribución Animal , Animales , Restos Mortales , Cambio Climático , Océanos y MaresRESUMEN
Domoic acid (DA)-producing harmful algal blooms (HABs) have been present at unprecedented geographic extent and duration in recent years causing an increase in contamination of seafood by this common environmental neurotoxin. The toxin is responsible for the neurotoxic illness, amnesic shellfish poisoning (ASP), that is characterized by gastro-intestinal distress, seizures, memory loss, and death. Established seafood safety regulatory limits of 20 µg DA/g shellfish have been relatively successful at protecting human seafood consumers from short-term high-level exposures and episodes of acute ASP. Significant concerns, however, remain regarding the potential impact of repetitive low-level or chronic DA exposure for which there are no protections. Here, we report the novel discovery of a DA-specific antibody in the serum of chronically-exposed tribal shellfish harvesters from a region where DA is commonly detected at low levels in razor clams year-round. The toxin was also detected in tribal shellfish consumers' urine samples confirming systemic DA exposure via consumption of legally-harvested razor clams. The presence of a DA-specific antibody in the serum of human shellfish consumers confirms long-term chronic DA exposure and may be useful as a diagnostic biomarker in a clinical setting. Adverse effects of chronic low-level DA exposure have been previously documented in laboratory animal studies and tribal razor clam consumers, underscoring the potential clinical impact of such a diagnostic biomarker for protecting human health. The discovery of this type of antibody response to chronic DA exposure has broader implications for other environmental neurotoxins of concern.
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Anticuerpos/sangre , Técnicas Biosensibles , Ácido Kaínico/análogos & derivados , Toxinas Marinas/inmunología , Neurotoxinas/inmunología , Monitoreo Biológico , Biomarcadores/sangre , Exposición Dietética/análisis , Humanos , Indígenas Norteamericanos , Ácido Kaínico/inmunología , Ácido Kaínico/orina , Toxinas Marinas/orina , Neurotoxinas/orina , Mariscos , Resonancia por Plasmón de Superficie , WashingtónRESUMEN
Domoic acid (DA) is a neuroexcitotoxic amino acid that is naturally produced by some species of marine diatoms during harmful algal blooms (HABs). The toxin is transferred through the food web from plantivorous fish and shellfish to marine mammals resulting in significant morbidity and mortality. Due to the timing and location of DA producing HABs, it is well documented that pregnant female California sea lions (CSL) are regularly exposed to DA through their diet thereby posing exposure risks to a neuroteratogen in developing fetuses. In the present study, fluids from 36 fetuses sampled from naturally exposed pregnant CSLs were examined for DA. Domoic acid was detected in 79% of amniotic fluid (nâ¯=â¯24), 67% of allantoic fluid (nâ¯=â¯9), 75% of urine (nâ¯=â¯4), 41% of meconium (nâ¯=â¯17) and 29% of stomach content (nâ¯=â¯21) samples opportunistically collected from CSL fetuses. The distribution of DA in fetal samples indicates an increased prenatal exposure risk due to recirculation of DA in fetal fluids and continuous exposure to the developing brain.
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Diatomeas/metabolismo , Floraciones de Algas Nocivas , Ácido Kaínico/análogos & derivados , Neurotoxinas/análisis , Leones Marinos/embriología , Líquido Amniótico/química , Animales , Diatomeas/química , Femenino , Feto/química , Cadena Alimentaria , Ácido Kaínico/análisis , Ácido Kaínico/toxicidad , Mamíferos , Neurotoxinas/toxicidad , Embarazo , RiesgoRESUMEN
Domoic acid (DA) is a neurotoxin produced during harmful algal blooms that accumulates in marine organisms that serve as food resources for humans. While acute DA neurotoxicity can cause seizures and hippocampal lesions, less is known regarding how chronic, subacute DA exposure in adulthood impacts the hippocampus. With more frequent occurrences of harmful algal blooms, it is important to understand the potential impact of repeated, low-level DA exposure on human health. To model repeated, low-dose DA exposure, adult mice received a single low-dose (0.75 ± 0.05 µg/g) of DA or vehicle weekly for 22 consecutive weeks. Quantitative immunohistochemistry was performed to assess the effects of repeated, low-level DA exposure on hippocampal cells and synapses. Vesicular glutamate transporter 1 (VGluT1) immunoreactivity within excitatory boutons in CA1 of DA-exposed mice was increased. Levels of other vesicular transporter proteins (i.e., VGluT2 and the vesicular GABA transporter (VGAT)) within boutons, and corresponding bouton densities, were not significantly altered in CA1, CA3, or dentate gyrus. There were no significant changes in neuron density or glial fibrillary acidic protein (GFAP) immunoreactivity following chronic, low-dose exposure. This suggests that repeated low doses of DA, unlike high doses of DA, do not cause neuronal loss or astrocyte activation in hippocampus in adult mice. Instead, these findings demonstrate that repeated exposure to low levels of DA leads to subtle changes in VGluT1 expression within CA1 excitatory boutons, which may alter glutamatergic transmission in CA1 and disrupt behaviors dependent on spatial memory.
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Ácido Kaínico/análogos & derivados , Neurotoxinas/toxicidad , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismo , Animales , Femenino , Floraciones de Algas Nocivas , Hipocampo/metabolismo , Humanos , Ácido Kaínico/toxicidad , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismoRESUMEN
Domoic Acid (DA) is a marine-based neurotoxin. Dietary exposure to high levels of DA via shellfish consumption has been associated with Amnesic Shellfish Poisoning, with milder memory decrements found in Native Americans (NAs) with repetitive, lower level exposures. Despite its importance for protective action, the clinical relevance of these milder memory problems remains unknown. The purpose of this study was to determine whether repeated, lower-level exposures to DA impact everyday memory (EM), i.e., the frequency of memory failures in everyday life. A cross-sectional sample of 60 NA men and women from the Pacific NW was studied with measures of dietary exposure to DA via razor clam (RC) consumption and EM. Findings indicated an association between problems with EM and elevated consumption of RCs with low levels of DA throughout the previous week and past year after controlling for age, sex, and education. NAs who eat a lot of RCs with presumably safe levels of DA are at risk for clinically significant memory problems. Public health outreach to minimize repetitive exposures are now in place and were facilitated by the use of community-based participatory research methods, with active involvement of state regulatory agencies, tribe leaders, and local physicians.
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Bivalvos , Exposición Dietética/efectos adversos , Ácido Kaínico/análogos & derivados , Toxinas Marinas/toxicidad , Memoria/efectos de los fármacos , Neurotoxinas/toxicidad , Intoxicación por Mariscos/epidemiología , Adolescente , Adulto , Anciano , Animales , Exposición Dietética/prevención & control , Femenino , Contaminación de Alimentos , Humanos , Ácido Kaínico/toxicidad , Masculino , Persona de Mediana Edad , Salud Pública , Investigación , Intoxicación por Mariscos/etiología , Adulto JovenRESUMEN
The consumption of one meal of seafood containing domoic acid (DA) at levels high enough to induce seizures can cause gross histopathological lesions in hippocampal regions of the brain and permanent memory loss in humans and marine mammals. Seafood regulatory limits have been set at 20mgDA/kg shellfish to protect human consumers from symptomatic acute exposure, but the effects of repetitive low-level asymptomatic exposure remain a critical knowledge gap. Recreational and Tribal-subsistence shellfish harvesters are known to regularly consume low levels of DA. The aim of this study was to determine if chronic low-level DA exposure, at doses below those that cause overt signs of neurotoxicity, has quantifiable impacts on cognitive function. To this end, female C57BL/6NJ mice were exposed to asymptomatic doses of DA (≈0.75mg/kg) or vehicle once a week for several months. Spatial learning and memory were tested in a radial water maze paradigm at one, six and 25 weeks of exposure, after a nine-week recovery period following cessation of exposure, and at three old age time points (18, 24 and 28 months old). Mice from select time points were also tested for activity levels in a novel cage environment using a photobeam activity system. Chronic low-level DA exposure caused significant spatial learning impairment and hyperactivity after 25 weeks of exposure in the absence of visible histopathological lesions in hippocampal regions of the brain. These cognitive effects were reversible after a nine-week recovery period with no toxin exposure and recovery was sustained into old age. These findings identify a new potential health risk of chronic low-level exposure in a mammalian model. Unlike the permanent cognitive impacts of acute exposure, the chronic low-level effects observed in this study were reversible suggesting that these deficits could potentially be managed through cessation of exposure if they also occur in human seafood consumers.
Asunto(s)
Disfunción Cognitiva/inducido químicamente , Ácido Kaínico/análogos & derivados , Aprendizaje/efectos de los fármacos , Toxinas Marinas/toxicidad , Alimentos Marinos/análisis , Memoria Espacial/efectos de los fármacos , Animales , Femenino , Hipocampo/anatomía & histología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Ácido Kaínico/toxicidad , Ratones , Ratones Endogámicos C57BL , Pruebas de Toxicidad CrónicaRESUMEN
Domoic acid (DA) is a neurotoxin that is naturally produced by phytoplankton and accumulates in seafood during harmful algal blooms. As the prevalence of DA increases in the marine environment, there is a critical need to identify seafood consumers at risk of DA poisoning. DA exposure was estimated in recreational razor clam (Siliqua patula) harvesters to determine if exposures above current regulatory guidelines occur and/or if harvesters are chronically exposed to low levels of DA. Human consumption rates of razor clams were determined by distributing 1523 surveys to recreational razor clam harvesters in spring 2015 and winter 2016, in Washington, USA. These consumption rate data were combined with DA measurements in razor clams, collected by a state monitoring program, to estimate human DA exposure. Approximately 7% of total acute exposures calculated (including the same individuals at different times) exceeded the current regulatory reference dose (0.075mgDA·kgbodyweight-1·d-1) due to higher than previously reported consumption rates, lower bodyweights, and/or by consumption of clams at the upper range of legal DA levels (maximum 20mg·kg-1 wet weight for whole tissue). Three percent of survey respondents were potentially at risk of chronic DA exposure by consuming a minimum of 15 clams per month for at 12 consecutive months. These insights into DA consumption will provide an additional tool for razor clam fishery management.
Asunto(s)
Bivalvos/química , Contaminación de Alimentos/análisis , Ácido Kaínico/análogos & derivados , Toxinas Marinas/análisis , Neurotoxinas/análisis , Adolescente , Adulto , Animales , Niño , Exposición Dietética , Femenino , Humanos , Ácido Kaínico/análisis , Ácido Kaínico/envenenamiento , Masculino , Toxinas Marinas/envenenamiento , Persona de Mediana Edad , Neurotoxinas/envenenamiento , Nivel sin Efectos Adversos Observados , Recreación , Encuestas y Cuestionarios , WashingtónRESUMEN
A coastwide bloom of the toxigenic diatom Pseudo-nitzschia in spring 2015 resulted in the largest recorded outbreak of the neurotoxin, domoic acid, along the North American west coast. Elevated toxins were measured in numerous stranded marine mammals and resulted in geographically extensive and prolonged closures of razor clam, rock crab, and Dungeness crab fisheries. We demonstrate that this outbreak was initiated by anomalously warm ocean conditions. Pseudo-nitzschia australis thrived north of its typical range in the warm, nutrient-poor water that spanned the northeast Pacific in early 2015. The seasonal transition to upwelling provided the nutrients necessary for a large-scale bloom; a series of spring storms delivered the bloom to the coast. Laboratory and field experiments confirming maximum growth rates with elevated temperatures and enhanced toxin production with nutrient enrichment, together with a retrospective analysis of toxic events, demonstrate the potential for similarly devastating ecological and economic disruptions in the future.