Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins.

David A Davis,Paul Alan Cox,Susan J Murch,Thomas M Coyne,Larry E Brand,Walter G Bradley,Kiyo Mondo,Deborah C Mash,Ama K Annor,Sarah Sharp,Misty E Niemeyer,Erica Stern,Susana Caballero

doi:10.1371/journal.pone.0213346

Abstract

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+ plaques and 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 cyanotoxin exposure and its potential impact on human health.

Highlights

Harmful algal blooms (HABs) are becoming increasingly frequent in fresh water lakes, estuaries, and the sea [1,2,3] likely due to climate warming and increased phosphorous and nitrogen effluents [2]
Epidemiological studies support a link between BMAA and neurodegenerative disease, since people living in close proximity of lakes with frequent cyanobacteria blooms have increased an incidence of Amyotrophic Lateral Sclerosis (ALS) [21,22,23,24,25]
Dolphin specimens in Massachusetts were obtained under a Stranding Agreement between National Ocean and Atmospheric Administration (NOAA) National Marine Fisheries Services Greater Atlantic Region Fisheries Office and International Fund for Animal Welfare (IFAW)

Summary

Introduction

Harmful algal blooms (HABs) are becoming increasingly frequent in fresh water lakes, estuaries, and the sea [1,2,3] likely due to climate warming and increased phosphorous and nitrogen effluents [2]. The cyanotoxin, β-N-methylamino-L-alanine (BMAA), has been linked to several neurodegenerative diseases [8,9,10,11]. Chronic dietary exposure to BMAA has been shown to trigger neurodegenerative changes in experimental models including non-human primates [15,16,17]. Epidemiological studies support a link between BMAA and neurodegenerative disease, since people living in close proximity of lakes with frequent cyanobacteria blooms have increased an incidence of ALS [21,22,23,24,25]. BMAA has been shown to accumulate in long-lived apex predators like sharks [26], as well as throughout the South Florida marine food web [27,28]

Methods

Results

Conclusion