TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA
Cetaceans are well-regarded as sentinels for toxin exposure. Emerging studies suggest that cetaceans can also develop neuropathological changes associated with neurodegenerative disease. The occurrence of neuropathology makes cetaceans an ideal species for examining the impact of marine toxins on th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/16/1/42 |
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| author | Susanna P. Garamszegi Daniel J. Brzostowicki Thomas M. Coyne Regina T. Vontell David A. Davis |
| author_facet | Susanna P. Garamszegi Daniel J. Brzostowicki Thomas M. Coyne Regina T. Vontell David A. Davis |
| author_sort | Susanna P. Garamszegi |
| collection | DOAJ |
| description | Cetaceans are well-regarded as sentinels for toxin exposure. Emerging studies suggest that cetaceans can also develop neuropathological changes associated with neurodegenerative disease. The occurrence of neuropathology makes cetaceans an ideal species for examining the impact of marine toxins on the brain across the lifespan. Here, we describe TAR DNA-binding protein 43 (TDP-43) proteinopathy and Alzheimer’s disease (AD) neuropathological changes in a beached harbor porpoise (<i>Phocoena phocoena</i>) that was exposed to a toxin produced by cyanobacteria called β-N-methylamino-L-alanine (BMAA). We found pathogenic TDP-43 cytoplasmic inclusions in neurons throughout the cerebral cortex, midbrain and brainstem. P62/sequestosome-1, responsible for the autophagy of misfolded proteins, was observed in the amygdala, hippocampus and frontal cortex. Genes implicated in AD and TDP-43 neuropathology such as <i>APP</i> and <i>TARDBP</i> were expressed in the brain. AD neuropathological changes such as amyloid-β plaques, neurofibrillary tangles, granulovacuolar degeneration and Hirano bodies were present in the hippocampus. These findings further support the development of progressive neurodegenerative disease in cetaceans and a potential causative link to cyanobacterial toxins. Climate change, nutrient pollution and industrial waste are increasing the frequency of harmful cyanobacterial blooms. Cyanotoxins like BMAA that are associated with neurodegenerative disease pose an increasing public health risk. |
| first_indexed | 2024-03-08T10:33:04Z |
| format | Article |
| id | doaj.art-0938b2fa54f342818fc60f3a06c3d5d0 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-08T10:33:04Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-0938b2fa54f342818fc60f3a06c3d5d02024-01-26T18:42:30ZengMDPI AGToxins2072-66512024-01-011614210.3390/toxins16010042TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAASusanna P. Garamszegi0Daniel J. Brzostowicki1Thomas M. Coyne2Regina T. Vontell3David A. Davis4Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USADepartment of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USACetaceans are well-regarded as sentinels for toxin exposure. Emerging studies suggest that cetaceans can also develop neuropathological changes associated with neurodegenerative disease. The occurrence of neuropathology makes cetaceans an ideal species for examining the impact of marine toxins on the brain across the lifespan. Here, we describe TAR DNA-binding protein 43 (TDP-43) proteinopathy and Alzheimer’s disease (AD) neuropathological changes in a beached harbor porpoise (<i>Phocoena phocoena</i>) that was exposed to a toxin produced by cyanobacteria called β-N-methylamino-L-alanine (BMAA). We found pathogenic TDP-43 cytoplasmic inclusions in neurons throughout the cerebral cortex, midbrain and brainstem. P62/sequestosome-1, responsible for the autophagy of misfolded proteins, was observed in the amygdala, hippocampus and frontal cortex. Genes implicated in AD and TDP-43 neuropathology such as <i>APP</i> and <i>TARDBP</i> were expressed in the brain. AD neuropathological changes such as amyloid-β plaques, neurofibrillary tangles, granulovacuolar degeneration and Hirano bodies were present in the hippocampus. These findings further support the development of progressive neurodegenerative disease in cetaceans and a potential causative link to cyanobacterial toxins. Climate change, nutrient pollution and industrial waste are increasing the frequency of harmful cyanobacterial blooms. Cyanotoxins like BMAA that are associated with neurodegenerative disease pose an increasing public health risk.https://www.mdpi.com/2072-6651/16/1/42blue green algae bloomcetacean strandingGuam ALS/PDCmarine neurotoxinmarine food webtoothed whales |
| spellingShingle | Susanna P. Garamszegi Daniel J. Brzostowicki Thomas M. Coyne Regina T. Vontell David A. Davis TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA Toxins blue green algae bloom cetacean stranding Guam ALS/PDC marine neurotoxin marine food web toothed whales |
| title | TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA |
| title_full | TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA |
| title_fullStr | TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA |
| title_full_unstemmed | TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA |
| title_short | TDP-43 and Alzheimer’s Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA |
| title_sort | tdp 43 and alzheimer s disease pathology in the brain of a harbor porpoise exposed to the cyanobacterial toxin bmaa |
| topic | blue green algae bloom cetacean stranding Guam ALS/PDC marine neurotoxin marine food web toothed whales |
| url | https://www.mdpi.com/2072-6651/16/1/42 |
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