Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins

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.

The Proposed Neurotoxin β-N-Methylamino-l-Alanine (BMAA) Is Taken up through Amino-Acid Transport Systems in the Cyanobacterium Anabaena PCC 7120

“…The neurotoxin β- N -methylamino- l -alanine (BMAA) is a non-protein amino acid, first identified from Cycas in 1967 [ 1 ]. Although the underlying mechanism is not understood, the accumulation of BMAA in brain tissues is found to be associated with neurodegenerative diseases such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease [ 2 , 3 , 4 , 5 ]. It is also postulated as one of the environmental factors that contribute to the relatively high rate of dementia in Finland [ 6 ].…”

Amyloid-beta peptide and phosphorylated tau in the frontopolar cerebral cortex and in the cerebellum of toothed whales: aging vs hypoxia

“…Based on these results, we present a novel hypothesis that considers hypoxia as one of the most important risk factors that could contribute to NDD in cetaceans, with special attention to BW, alongside to other proposed risk factors/causes proposed by other authors ( Davis et al, 2019 ; Di Guardo, 2018a , 2019 ; Fernández et al, 2017 ; Gunn-Moore et al, 2017 ) ( Fig. 3 ).…”

“…On the other hand, well-defined NFT were observed in the frontal and parietal cortex, thalamus and cerebellum of one bottlenose dolphin and three striped dolphins ( Stenella coeruleoalba ) ( Gunn-Moore et al, 2017 ). Aβ plaques were also observed in the striped dolphin, bottlenose dolphin, and common dolphin ( Delphinus delphis ) ( Davis et al, 2019 ; Gunn-Moore et al, 2017 ; Stylianaki et al, 2019 ).…”

“…The maximum-recorded lifespan in the killer whale ( Orcinus orca ) is 78 years, in the short-finned pilot whale it is 63 years, and in the striped dolphin it is 58 years ( Foster et al, 2012 ; Gunn-Moore et al, 2017 ). Recent studies have drawn some novel attention to neurodegenerative diseases (NDD) in cetaceans and it has been suggested that dolphins might be one of the very few potential natural models of AD ( Davis et al, 2019 ; Di Guardo, 2018a , b , 2019 ; Gunn-Moore et al, 2017 ; Sacchini et al, 2018 ; Sarasa and Pesini, 2009 ; Stylianaki et al, 2019 ). Positive labelling to τ was observed in the cytoplasm of neurons of deep cortical areas of frontal, parietal and temporal lobe of one bottlenose dolphin ( Tursiops truncatus ) with no clear NFT ( Stylianaki et al, 2019 ).…”

Agricultural Nitrogen Budget for a Long-Term Row Crop Production System in the Midwest USA

“…also favored the growth of cyanobacterial HABs and release of cyanotoxins, which subsequently caused a threat to aquatic animals (pelicans, turtles, manatees, fish, sea lions, etc.) including an Alzheimer's like disease in Dolphins [7]. High concentrations of NO 3 -N in drinking water are reported to cause human health problems such as methemoglobinemia or blue baby syndrome in infants, gastric cancer in adults [8][9][10][11], and linkages to non-Hodgkin's Lymphoma [12,13].…”