BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure.
BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure.
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DOI：
10.3390/toxins13100697
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发表时间：
2021-10-01
期刊：
影响因子：
4.2
通讯作者：
Cox PA
中科院分区：
文献类型：
--
作者：
Davis DA;Garamszegi SP;Banack SA;Dooley PD;Coyne TM;McLean DW;Rotstein DS;Mash DC;Cox PA
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.
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影响因子：
2.4
作者：
Bossart, G. D.
通讯作者：
Bossart, G. D.
DOI：
10.1098/rspb.2015.2397
发表时间：
2016-01-27
期刊：
Proceedings. Biological sciences
影响因子：
--
作者：
Cox PA;Davis DA;Mash DC;Metcalf JS;Banack SA
通讯作者：
Banack SA
影响因子：
9.9
作者：
Cox, PA;Sacks, OW
通讯作者：
Sacks, OW
DOI：
10.1073/pnas.2235808100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Cox, PA;Banack, SA;Murch, SJ
通讯作者：
Murch, SJ
影响因子：
--
作者：
Bell, E. Arthur
通讯作者：
Bell, E. Arthur