Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins

Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins
David A. Davis, Kiyo Mondo, Erica Stern,Ama K. Annor, Susan J. Murch, Thomas M. Coyne, Deborah C. Mash Published: March 20, 2019

https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0213346#sec017

Dolphin stranding events occur frequently in Florida and Massachusetts. Dolphins are an excellent sentinel species for toxin exposures in the marine environment. In this report we examine whether cyanobacterial neurotoxin, β-methylamino-L-alanine (BMAA), is present in stranded dolphins. BMAA has been shown to bioaccumulate in the marine food web, including in the muscles and fins of sharks. Dietary exposure to BMAA is associated with the occurrence of neurofibrillary tangles and β-amyloid plaques in nonhuman primates. The findings of protein-bound BMAA in brain tissues from patients with Alzheimer’s disease has advanced the hypothesis that BMAA may be linked to dementia.

Since dolphins are apex predators and consume prey containing high amounts of BMAA, we examined necropsy specimens to determine if dietary and environmental exposures may result in the accumulation of BMAA in the brains of dolphins. To test this hypothesis, we measured BMAA in a series of brains collected from dolphins stranded in Florida and Massachusetts using two orthogonal analytical methods: 1) high performance liquid chromatography, and 2) ultra-performance liquid chromatography with tandem mass spectrometry. We detected high levels of BMAA (20–748 μg/g) in the brains of 13 of 14 dolphins. To correlate neuropathological changes with toxin exposure, gross and microscopic examinations were performed on cortical brain regions responsible for acoustico-motor navigation. We observed increased numbers of β-amyloid+plaquesand dystrophic neurites in the auditory cortex compared to the visual cortex and brainstem. The presence of BMAA and neuropathological changes in the stranded dolphin brain may help to further our understanding of cyanotoxinexposure and its potential impact on human health.

As the world’s climate warms, HABs are becoming more frequent, including in eastern China, which has seen some of the largest cyanobacterial blooms on Earth, and North America. Cyanobacteria produce powerful cyanotoxinsthat impact aquatic and terrestrial life. Exposures to cyanotoxins are a public health concern as they are linked to organ system damage and disease. Examining the levels of the cyanobacterial toxin BMAA in apex predators, such as dolphins and sharks, provides a powerful bio-indicator of the potential for human exposures [26,27,49].

BMAA is produced by cyanobacteria that are sometimes seen as surface blooms, but can occur in the water column and in benthic mats in lakes, shallow estuaries and bays. In marine systems, BMAA enters the food chain via crustaceans and bottom-feeding fish, and then accumulates into long-lived apex predators like sharks [26,27]. We now report that another apex predator, dolphins, when exposed to cyanobacteria or diets of crustaceans and fish containing BMAA, bioaccumulate the toxin in their neuroproteins. In our study, BMAA was present in the brains of stranded dolphins at 1.4-fold greater amounts than in the brains of patients with AD and ALS [18]. Dolphins beached in Florida were observed to have nearly 3-fold higher concentrations of BMAA in their brains than dolphins beached in Massachusetts. The differences in BMAA concentration may be due to differences in diet, occurrences of algal blooms, varying phytoplankton species or modes of stranding [56].

The recognition that the very high incidence of neurodegenerative disease Guam ALS/PDC was likely due to the production of BMAA by endophytic cyanobacteria resident in specialized coralloid roots of cycad trees led to the hypothesis that BMAA is a cause of ALS/PDC and non-endemic ALS, and provided a link to neurodegenerative disorders [19,20]. In Guam, cycad seeds contain BMAA and are used to make flour by the indigenous Chamorro. BMAA is also biomagnified up the food chain to animals like pigs, deer and flying foxes that are part of the Chamorro diet [20,50,57]. Once ingested, BMAA can cross the blood-brain barrier and become incorporated into proteins where it is associated with neuropathological changes as seen in Guam ALS/PDC [12,20]. In this paper, we have now shown that BMAA is detectable in brains of dolphins that also show neuropathological changes characteristic of human neurodegenerative disease. Here, BMAA is also shown to accumulate with increasing length and age class. Thus, our data suggest dolphins may provide a naturalistic model of BMAA toxin exposures in marine environments. The effects of this exposure however are not yet clear.

Conclusion
We have detected BMAA in the cerebral cortex of stranded dolphins. We also report Alzheimer-like neurodegenerative changes in the brains of dolphins containing BMAA. The presence of BMAA suggests that dolphins provide an excellent sentinel species for toxin exposures in the marine environment.