Spatiotemporal distribution of neurotoxin ß-N-methylamino-L-alanine and 2,4-diaminobutyric acid in offshore aquaculture area of Shandong province, China.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) has been widely detected in aquatic environments and got the public's attention due to its potential risk to human neurodegenerative diseases. Three cruises in spring, summer and autumn seasons were carried out in Laizhou Bay (LZB), Sishili Bay (SSLB), Sanggou Bay (SGB), Jiaozhou Bay (JZB) and Haizhou Bay (HZB) in 2023. Results showed that the temporal distribution pattern of BMAA in plankton varied in the survey bays. In LZB, the highest average concentration of BMAA in phytoplankton occurred in spring. The highest average concentration of BMAA in phytoplankton was detected in summer in SSLB, JZB and HZB. However, BMAA was only detected in phytoplankton at the R2 station in SGB in spring. The highest average concentration of BMAA in zooplankton was observed in spring in LZB, SSLB and SGB. Zooplankton accumulated the highest average concentration of BMAA in JZB and HZB in summer and autumn, respectively. The BMAA was widely detected in marine mollusks throughout the investigative period. In addition, Mantel test and RDA analysis results indicated that DIN/DIP strongly impacted on the spatiotemporal distribution of BMAA in phytoplankton, in JZB and SSLB. The spatiotemporal distribution of BMAA in plankton was correlated with temperature and DO in JZB. More field cruises should be conducted to explore the environmental drivers of the neurotoxin BMAA in marine ecosystems in future studies.

Activation of retinoid X receptors protects retinal neurons and pigment epithelial cells from BMAA-induced death.

Exposure to the non-protein amino acid cyanotoxin ß-N-methylamino-L-alanine (BMAA), released by cyanobacteria found in many water reservoirs has been associated with neurodegenerative diseases. We previously demonstrated that BMAA induced cell death in both retina photoreceptors (PHRs) and amacrine neurons by triggering different molecular pathways, as activation of NMDA receptors and formation of carbamate-adducts was only observed in amacrine cell death. We established that activation of Retinoid X Receptors (RXR) protects retinal cells, including retina pigment epithelial (RPE) cells from oxidative stress-induced apoptosis. We now investigated the mechanisms underlying BMAA toxicity in these cells and those involved in RXR protection. BMAA addition to rat retinal neurons during early development in vitro increased reactive oxygen species (ROS) generation and polyADP ribose polymers (PAR) formation, while pre-treatment with serine (Ser) before BMAA addition decreased PHR death. Notably, RXR activation with the HX630 agonist prevented BMAA-induced death in both neuronal types, reducing ROS generation, preserving mitochondrial potential, and decreasing TUNEL-positive cells and PAR formation. This suggests that BMAA promoted PHR death by substituting Ser in polypeptide chains and by inducing polyADP ribose polymerase activation. BMAA induced cell death in ARPE-19 cells, a human epithelial cell line; RXR activation prevented this death, decreasing ROS generation and caspase 3/7 activity. These findings suggest that RXR activation prevents BMAA harmful effects on retinal neurons and RPE cells, supporting this activation as a broad-spectrum strategy for treating retina degenerations.

ß-N-methylamino-L-alanine production, photosynthesis and transcriptional expression in a possible mutation strain and a wild strain of Thalassiosira minima.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) produced by marine diatoms has been implicated as an important environmental trigger of neurodegenerative diseases in humans. However, the biosynthesis mechanism of BMAA in marine diatoms is still unknown. In the present study, the strain of diatom Thalassiosira minima almost lost the biosynthesis ability for BMAA after a long-term subculture in our laboratory. The production of BMAA-containing proteins in the mutant strain of T. minima reduced to 18.2 % of that in the wild strain, meanwhile the cell size decreased but pigment content increased in the mutant strain. Take consideration of our previous transcriptional data on the mixed diatom and cyanobacterium cultures, the current transcriptome analysis showed four identical and highly correlated KEGG pathways associated with the accumulation of misfolded proteins in diatom, including ribosome, proteasome, SNARE interactions in vesicle transport, and protein processing in the endoplasmic reticulum. Analysis of amino acids and transcriptional information suggested that amino acid synthesis and degradation are associated with the biosynthesis of BMAA-containing proteins. In addition, a reduction in the precision of ubiquitination-mediated protein hydrolysis and vesicular transport by the COPII system will exacerbate the accumulation of BMAA-containing proteins in diatoms.

Cyanotoxin accumulation and growth patterns of biocrust communities under variable environmental conditions.

Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a(S) (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient. In contrast to previous work, we showed that hydration had an overall positive effect on growth and toxin accumulation, that nitrogen was not correlated with growth or toxin production, and that phosphorus enrichment negatively affected AEG and BMAA concentrations. Excess illumination positively correlated with AEG, and negatively correlated with all other toxins and growth. Basic pH negatively affected only the accumulation of BMAA. Anatoxin-a(S) (guanitoxin) was not correlated with any tested variables, while microcystins were not detected in any of the samples. Concerning toxin pools, AEG and BMAA were good predictors of the presence of one another. In a newly conceptualized scheme, we integrate aspects of biocrust growth and toxin pool accumulations with arid-relevant desertification drivers.

The role of neutrophil extracellular traps in ß-methylamino L-alanine-induced liver injury in mice.

The non-protein amino acid ß-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a 'double-edged sword' for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.

Microbial Diversity Impacts Non-Protein Amino Acid Production in Cyanobacterial Bloom Cultures Collected from Lake Winnipeg.

Lake Winnipeg in Manitoba, Canada is heavily impacted by harmful algal blooms that contain non-protein amino acids (NPAAs) produced by cyanobacteria: N-(2-aminoethyl)glycine (AEG), ß-aminomethyl-L-alanine (BAMA), ß-N-methylamino-L-alanine (BMAA), and 2,4-diaminobutyric acid (DAB). Our objective was to investigate the impact of microbial diversity on NPAA production by cyanobacteria using semi-purified crude cyanobacterial cultures established from field samples collected by the Lake Winnipeg Research Consortium between 2016 and 2021. NPAAs were detected and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) using validated analytical methods, while Shannon and Simpson alpha diversity scores were determined from 16S rRNA metagenomic sequences. Alpha diversity in isolate cultures was significantly decreased compared to crude cyanobacterial cultures (p < 0.001), indicating successful semi-purification. BMAA and AEG concentrations were higher in crude compared to isolate cultures (p < 0.0001), and AEG concentrations were correlated to the alpha diversity in cultures (r = 0.554; p < 0.0001). BAMA concentrations were increased in isolate cultures (p < 0.05), while DAB concentrations were similar in crude and isolate cultures. These results demonstrate that microbial community complexity impacts NPAA production by cyanobacteria and related organisms.

Impact of the neurotoxin ß-N-methylamino-L-alanine on the diatom Thalassiosira pseudonana using metabolomics.

The neurotoxin ß-N-methylamino-L-alanine (BMAA) has emerged as an environmental factor related to neurodegenerative diseases. BMAA is produced by various microorganisms including cyanobacteria and diatoms, in diverse ecosystems. In the diatom Phaeodactylum tricornutum, BMAA is known to inhibit growth. The present study investigated the impact of BMAA on the diatom Thalassiosira pseudonana by exposing it to different concentrations of exogenous BMAA. Metabolomics was predominantly employed to investigate the effect of BMAA on T. pseudonana, and MetaboAnalyst (https://www.metabo-analyst.ca/) was used to identify BMAA-associated metabolisms/pathways in T. pseudonana. Furthermore, to explore the unique response, specific metabolites were compared between treatments. When the growth was obstructed by BMAA, 17 metabolisms/pathways including nitrogen and glutathione (i.e. oxidative stress) metabolisms, were influenced in T. pseudonana. This study has further determined that 11 out of 17 metabolisms/pathways could be essentially affected by BMAA, leading to the inhibition of diatom growth.

Presence of the neurotoxin ß-N-methylamino-L-alanine in irrigation water and accumulation in cereal grains with human exposure risk.

The present study demonstrates the presence of the neurotoxin ß-N-methylamino-L-alanine and its cyanobacterial producers in irrigation water and grains of some cereal plants from farmlands irrigated with Nile River water in Egypt. BMAA detected by LC-MS/MS in phytoplankton samples was found at higher concentrations of free form (0.84-11.4 µg L-1) than of protein-bound form (0.16-1.6 µg L-1), in association with the dominance of cyanobacteria in irrigation water canals. Dominant cyanobacterial species isolated from these irrigation waters including Aphanocapsa planctonica, Chroococcus minutus, Dolichospermum lemmermanni, Nostoc commune, and Oscillatoria tenuis were found to produce different concentrations of free (4.8-71.1 µg g-1 dry weight) and protein-bound (0.1-11.4 µg g-1 dry weight) BMAA. In the meantime, BMAA was also detected in a protein-bound form only in grains of corn (3.87-4.51 µg g-1 fresh weight) and sorghum (5.1-7.1 µg g-1 fresh weight) plants, but not in wheat grains. The amounts of BMAA accumulated in these grains correlated with BMAA concentrations detected in relevant irrigation water canals. The presence of BMAA in cereal grains would constitute a risk to human and animal health upon consumption of contaminated grains. The study, therefore, suggests continuous monitoring of BMAA and other cyanotoxins in irrigation waters and edible plants to protect the public against exposure to such potent toxins.

Evaluation of cyanotoxin L-BMAA effect on α-synuclein and TDP43 proteinopathy.

The complex interplay between genetic and environmental factors is considered the cause of neurodegenerative diseases including Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). Among the environmental factors, toxins produced by cyanobacteria have received much attention due to the significant increase in cyanobacteria growth worldwide. In particular, L-BMAA toxin, produced by diverse taxa of cyanobacteria, dinoflagellates and diatoms, has been extensively correlated to neurodegeneration. The molecular mechanism of L-BMAA neurotoxicity is still cryptic and far from being understood. In this research article, we have investigated the molecular pathways altered by L-BMAA exposure in cell systems, highlighting a significant increase in specific stress pathways and an impairment in autophagic processes. Interestingly, these changes lead to the accumulation of both α-synuclein and TDP43, which are correlated with PD and ALS proteinopathy, respectively. Finally, we were able to demonstrate specific alterations of TDP43 WT or pathological mutants with respect to protein accumulation, aggregation and cytoplasmic translocation, some of the typical features of both sporadic and familial ALS.

How does the neurotoxin ß-N-methylamino-L-alanine exist in biological matrices and cause toxicity?

The neurotoxin ß-N-methylamino-L-alanine (BMAA) has been deemed as a risk factor for some neurodegenerative diseases such as amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC). This possible link has been proved in some primate models and cell cultures with the appearance that BMAA exposure can cause excitotoxicity, formation of protein aggregates, and/or oxidative stress. The neurotoxin BMAA extensively exists in the environment and can be transferred through the food web to human beings. In this review, the occurrence, toxicological mechanisms, and characteristics of BMAA were comprehensively summarized, and proteins and peptides were speculated as its possible binding substances in biological matrices. It is difficult to compare the published data from previous studies due to the inconsistent analytical methods and components of BMAA. The binding characteristics of BMAA should be focused on to improve our understanding of its health risk to human health in the future.

Protection against ß-N-methylamino-l-alanineꟷinduced vesicular monoamine transporter 2 inhibition by hydroxyl-containing proteinogenic amino acids.

ß-N-methylamino-l-alanine (BMAA) has been shown to inhibit vesicular monoamine transporter 2 (VMAT2), thereby preventing the uptake of monoaminergic neurotransmitters into platelet dense granules and synaptic vesicles. The inhibition is hypothesized to be through direct association of BMAA with hydroxyl groupꟷcontaining amino acid residues in VMAT2. This study evaluated whether BMAA-induced inhibition of VMAT2 could be prevented directly by co-incubation of BMAA with amino acids, and if this protection was specific for BMAA inhibition of VMAT2. l-tyrosine, and to a lesser extent l-serine, was able to prevent BMAA-induced VMAT2 inhibition in a concentration-dependent manner, whereas neither l-threonine nor amino acids without side chain hydroxyl groups could reduce this inhibition. Reserpine-induced VMAT2 inhibition was unaffected by any of the amino acids. These data support the hypothesized interaction between BMAA and hydroxyl groupꟷcontaining amino acids and suggests that this interaction might be leveraged to protect against the toxicity of BMAA.

Uptake of ß-N-methylamino-L-alanine (BMAA) into glutamate-specific synaptic vesicles: Exploring the validity of the excitotoxicity mechanism of BMAA.

The first mechanism of toxicity proposed for the cyanobacterial neurotoxin ß-N-methylamino-L-alanine (BMAA) was excitotoxicity, and this was supported by numerous in vitro studies in which overactivation of both ionotropic and metabotropic glutamate receptors was reported. However, the excitotoxicity of BMAA is weak in comparison with other known excitotoxins and on par with that of glutamate, implying that to achieve sufficient synaptic concentrations of BMAA to cause classical in vivo excitotoxicity, BMAA must either accumulate in synapses to allow persistent glutamate receptor activation or it must be released in sufficiently high concentrations into synapses to cause the overexcitation. Since it has been shown that BMAA can be readily removed from synapses, release of high concentrations of BMAA into synapses must be shown to confirm its role as an excitotoxin in in vivo systems. This study therefore sought to evaluate the uptake of BMAA into synaptic vesicles and to determine if BMAA affects the uptake of glutamate into synaptic vesicles. There was no evidence to support uptake of BMAA into glutamate-specific synaptic vesicles but there was some indication that BMAA may affect the uptake of glutamate into synaptic vesicles. The uptake of BMAA into synaptic vesicles isolated from areas other than the cerebral cortex should be investigated before definite conclusions can be drawn about the role of BMAA as an excitotoxin.

A Direct Analysis of ß-N-methylamino-l-alanine Enantiomers and Isomers and Its Application to Cyanobacteria and Marine Mollusks.

Of the wide variety of toxic compounds produced by cyanobacteria, the neurotoxic amino acid ß-N-methylamino-l-alanine (BMAA) has attracted attention as a result of its association with chronic human neurodegenerative diseases such as ALS and Alzheimer's. Consequently, specific detection methods are required to assess the presence of BMAA and its isomers in environmental and clinical materials, including cyanobacteria and mollusks. Although the separation of isomers such as ß-amino-N-methylalanine (BAMA), N-(2-aminoethyl)glycine (AEG) and 2,4-diaminobutyric acid (DAB) from BMAA has been demonstrated during routine analysis, a further compounding factor is the potential presence of enantiomers for some of these isomers. Current analytical methods for BMAA mostly do not discriminate between enantiomers, and the chiral configuration of BMAA in cyanobacteria is still largely unexplored. To understand the potential for the occurrence of D-BMAA in cyanobacteria, a chiral UPLC-MS/MS method was developed to separate BMAA enantiomers and isomers and to determine the enantiomeric configuration of endogenous free BMAA in a marine Lyngbya mat and two mussel reference materials. After extraction, purification and derivatization with N-(4-nitrophenoxycarbonyl)-l-phenylalanine 2-methoxyethyl ester ((S)-NIFE), both L- and D-BMAA were identified as free amino acids in cyanobacterial materials, whereas only L-BMAA was identified in mussel tissues. The finding of D-BMAA in biological environmental materials raises questions concerning the source and role of BMAA enantiomers in neurological disease.

Effects of the Toxic Non-Protein Amino Acid ß-Methylamino-L-Alanine (BMAA) on Intracellular Amino Acid Levels in Neuroblastoma Cells.

The cyanobacterial non-protein amino acid (AA) ß-Methylamino-L-alanine (BMAA) is considered to be a neurotoxin. BMAA caused histopathological changes in brains and spinal cords of primates consistent with some of those seen in early motor neuron disease; however, supplementation with L-serine protected against some of those changes. We examined the impact of BMAA on AA concentrations in human neuroblastoma cells in vitro. Cells were treated with 1000 µM BMAA and intracellular free AA concentrations in treated and control cells were compared at six time-points over a 48 h culture period. BMAA had a profound effect on intracellular AA levels at specific time points but in most cases, AA homeostasis was re-established in the cell. The most heavily impacted amino acid was serine which was depleted in BMAA-treated cells from 9 h onwards. Correction of serine depletion could be a factor in the observation that supplementation with L-serine protects against BMAA toxicity in vitro and in vivo. AAs that could potentially be involved in protection against BMAA-induced oxidation such as histidine, tyrosine, and phenylalanine were depleted in cells at later time points.

Simultaneous Analysis of Cyanotoxins ß-N-methylamino-L-alanine (BMAA) and Microcystins-RR, -LR, and -YR Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

ß-N-methylamino-L-alanine (BMAA) and its isomers, 2,4-diaminobutyric acid (2,4-DAB) and N-(2-aminoethyl)-glycine (AEG), along with microcystins (MCs)-RR, -LR, and -YR (the major MC congeners), are cyanotoxins that can cause detrimental health and environmental impacts during toxic blooms. Currently, there are no reverse-phase (RP) LC-MS/MS methods for the simultaneous detection and quantification of BMAA, its isomers, and the major MCs in a single analysis; therefore, multiple analyses are required to assess the toxic load of a sample. Here, we present a newly developed and validated method for the detection and quantification of BMAA, 2,4-DAB, AEG, MC-LR, MC-RR, and MC-YR using RP LC-MS/MS. Method validation was performed, assessing linearity (r2 > 0.996), accuracy (>90% recovery for spiked samples), precision (7% relative standard deviation), and limits of detection (LODs) and quantification (LOQs) (ranging from 0.13 to 1.38 ng mL-1). The application of this combined cyanotoxin analysis on a culture of Microcystis aeruginosa resulted in the simultaneous detection of 2,4-DAB (0.249 ng mg-1 dry weight (DW)) and MC-YR (4828 ng mg-1 DW). This study provides a unified method for the quantitative analysis of BMAA, its isomers, and three MC congeners in natural environmental samples.

Chronic exposure to l-BMAA cyanotoxin induces cytoplasmic TDP-43 accumulation and glial activation, reproducing an amyotrophic lateral sclerosis-like phenotype in mice.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and often fatal neurodegenerative disease characterized by the loss of Motor Neurons (MNs) in spinal cord, motor cortex and brainstem. Despite significant efforts in the field, the exact pathogenetic mechanisms underlying both familial and sporadic forms of ALS have not been fully elucidated, and the therapeutic possibilities are still very limited. Here we investigate the molecular mechanisms of neurodegeneration induced by chronic exposure to the environmental cyanotoxin L-BMAA, which causes a form of ALS/Parkinson's disease (PD) in several populations consuming food and/or water containing high amounts of this compound. METHODS: In this effort, mice were chronically exposed to L-BMAA and analyzed at different time points to evaluate cellular and molecular alterations and behavioral deficits, performing MTT assay, immunoblot, immunofluorescence and immunohistochemistry analysis, and behavioral tests. RESULTS: We found that cyanotoxin L-BMAA determines apoptotic cell death and a marked astrogliosis in spinal cord and motor cortex, and induces neurotoxicity by favoring TDP-43 cytoplasmic accumulation. CONCLUSIONS: Overall, our results characterize a new versatile neurotoxic animal model of ALS that may be useful for the identification of new druggable targets to develop innovative therapeutic strategies for this disease.

Raw Water and ALS: A Unifying Hypothesis for the Environmental Agents Involved in ALS.

Different studies identified the presence of several altered genes in familial and sporadic amyotrophic lateral sclerosis (ALS) forms. The experimental data, together with the epidemiological data, would seem to suggest the existence of molecular mechanisms (e.g., axonal transport) related to these genes, together with a susceptibility of the same genes to certain environmental factors that would therefore suggest an impact of the environment on the etiopathogenesis of ALS. In our review, we considered the most relevant environmental clusters around the world, collecting different hypotheses and underlining common environmental factors among the different clusters. Moreover, further epidemiological data identified a higher risk of ALS in professional athletes and, in particular, in soccer and football players. Despite this increased risk of ALS highlighted by the epidemiological evidence in aforementioned sports, the mechanisms remain unclear. At last, the use of raw water has been associated with ALS risk. The aim of the present review is to characterize a possible relationship between these clusters, to be explored in the context of the interaction between genetic and environmental factors on the etiopathogenesis of ALS.

Five Years Monitoring the Emergence of Unregulated Toxins in Shellfish in France (EMERGTOX 2018-2022).

Shellfish accumulate microalgal toxins, which can make them unsafe for human consumption. In France, in accordance with EU regulations, three groups of marine toxins are currently under official monitoring: lipophilic toxins, saxitoxins, and domoic acid. Other unregulated toxin groups are also present in European shellfish, including emerging lipophilic and hydrophilic marine toxins (e.g., pinnatoxins, brevetoxins) and the neurotoxin ß-N-methylamino-L-alanine (BMAA). To acquire data on emerging toxins in France, the monitoring program EMERGTOX was set up along the French coasts in 2018. Three new broad-spectrum LC-MS/MS methods were developed to quantify regulated and unregulated lipophilic and hydrophilic toxins and the BMAA group in shellfish (bivalve mollusks and gastropods). A single-laboratory validation of each of these methods was performed. Additionally, these specific, reliable, and sensitive operating procedures allowed the detection of groups of EU unregulated toxins in shellfish samples from French coasts: spirolides (SPX-13-DesMeC, SPX-DesMeD), pinnatoxins (PnTX-G, PnTX-A), gymnodimines (GYM-A), brevetoxins (BTX-2, BTX-3), microcystins (dmMC-RR, MC-RR), anatoxin, cylindrospermopsin and BMAA/DAB. Here, we present essentially the results of the unregulated toxins obtained from the French EMERGTOX monitoring plan during the past five years (2018-2022). Based on our findings, we outline future needs for monitoring to protect consumers from emerging unregulated toxins.

The Effects of Long-term, Low-dose ß-N-methylamino-L-alanine (BMAA) Exposures in Adult SODG93R Transgenic Zebrafish.

ß-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease. We used a transgenic zebrafish with an ALS-associated mutation, compared with wild-type fish to explore the potential neurotoxic effects of BMAA through chronic long-term exposures. While our results revealed low concentrations of BMAA in the brains of exposed fish, we found no evidence of decreased swim performance or behavioral differences that might be reflective of neurodegenerative disease. Further research is needed to determine if chronic BMAA exposure in adult zebrafish is a suitable model to study neurodegenerative disease initiation and/or progression.

Effects of developmental exposure to neurotoxic algal metabolites on predator-prey interactions in larval Pimephales promelas.

Harmful algal blooms are a growing environmental concern in aquatic systems. Although it is known that some of the secondary metabolites produced by cyanobacteria can alter predator-prey dynamics in aquatic communities by reducing foraging and/or predator evasion success, the mechanisms underpinning such responses are largely unknown. In this study, we examined the effects of a potent algal neurotoxin, ß-N-methylamino-L-alanine (BMAA), on the development and behavior of larval Fathead Minnows, Pimephales promelas, during predator-prey interactions. We exposed eggs and larvae to environmentally relevant concentrations of BMAA for 21 days, then tested subjects in prey-capture and predator-evasion assays designed to isolate the effects of exposure at sequential points of the stimulus-response pathway. Exposure was associated with changes in the ability of larvae to detect and respond to environmental stimuli (i.e., a live prey item and a simulated vibrational predator), as well as changes in behavior and locomotor performance during the response. Our findings suggest that chronic exposure to neurodegenerative cyanotoxins could alter the outcomes of predator-prey interactions in natural systems by impairing an animal's ability to perceive, process, and respond to relevant biotic stimuli.