Bmaa, methylmercury, and mechanisms of neurodegeneration in dolphins: A natural model of toxin exposure

David A. Davis, Susanna P. Garamszegi, Sandra Anne Banack, Patrick D. Dooley, Thomas M. Coyne, Dylan W. McLean, David S. Rotstein, Deborah C. Mash, Paul Alan Cox

Research output: Contribution to journalArticlepeer-review

Abstract

Dolphins are well-regarded sentinels for toxin exposure and can bioaccumulate a cyanotoxin called β-N-methylamino-L-alanine (BMAA) that has been linked to human neurodegenerative disease. The same dolphins also possessed hallmarks of Alzheimer’s disease (AD), suggesting a possible association between toxin exposure and neuropathology. However, the mechanisms of neurodegeneration in dolphins and the impact cyanotoxins have on these processes are unknown. Here, we evaluate BMAA exposure by investigating transcription signatures using PCR for dolphin genes homologous to those implicated in AD and related dementias: APP, PSEN1, PSEN2, MAPT, GRN, TARDBP, and C9orf72. Immunohistochemistry and Sevier Münger silver staining were used to validate neuropathology. Methylmercury (MeHg), a synergistic neurotoxicant with BMAA, was also measured using PT-GC-AFS. We report that dolphins have up to a three-fold increase in gene transcription related to Aβ+ plaques, neurofibrillary tangles, neuritic plaques, and TDP-43+ intracytoplasmic inclusions. The upregulation of gene transcription in our dolphin cohort paralleled increasing BMAA concentration. In addition, dolphins with BMAA exposures equivalent to those reported in AD patients displayed up to a 14-fold increase in AD-type neuropathology. MeHg was detected (0.16–0.41 µg/g) and toxicity associated with exposure was also observed in the brain. These results demonstrate that dolphins develop neuropathology associated with AD and exposure to BMAA and MeHg may augment these processes.

Original languageEnglish (US)
Article number697
JournalToxins
Volume13
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • Alzheimer’s disease
  • Animal models
  • Anthropogenic contaminates
  • Blue-green algae
  • Cetaceans
  • Cyanotoxins
  • Neurofibrillary tangles
  • TDP-43

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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