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The Evaluation of BMAA Inhalation as a Potential Exposure Route Using a rat Model

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Abstract

Chronic inhalation of aerosolized β-N-methylamino-L-alanine (BMAA) could serve as potenital route for exposure to this cyanobacterial neurotoxin implicated in the development of neurodegenerative disease. We investigated environmental aerosol BMAA loads and the fate of inhaled isotopically labeled aerosolized BMAA in adult male Sprague Dawley rats, with doses corresponding to chronic aerosolized environmental BMAA exposure of over 65 days and up to 266 years. Environmental BMAA aerosol concentrations ranged from 6–39 pg L¯1. No clinical signs of toxicity were observed in rats exposed to aerosol containing BMAA at concentrations far exceeding the maximum recorded environmental BMAA aerosol load. Surprisingly, no labeled BMAA was observed in the brain, liver or lung tissues of exposed rats. However, a dose-dependent reduction in the Gln:Glu ratio was observed in brain and liver tissues together with an increase in 2,3 diaminopropanoic acid,15N2, the demethylated L-BMAA-4,4,4-d3,15N2 product, in liver tissues. This confirmed both BMAA uptake and distribution throughout the body. The increase in 2,3 diaminopropanoic acid,15N2 did however not account for the total loss of administered L-BMAA-4,4,4-d3,15N2 and thus, the absence of detectable L-BMAA-4,4,4-d3,15N2 in tissues and feces, together with the absence of other known BMAA catabolites, N-acetylated BMAA and methylamine, additional metabolic reactions are indicated. Significant biochemical responses to BMAA were only observed in doses corresponding to an unrealistic chronic exposure timeframe, suggesting that the inhalation of environmental levels of aerosolized BMAA might not be sufficient to elicit a biochemical response in adults.

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Acknowledgements

The authors acknowledge the National Research Foundation of South Africa for financial support. The authors would also like to acknowledge Leopold Ilag and Nadezda Zguna of the Department of Environmental Science and Analytical Chemistry, Stockholm University, for the use of equipment used in environmental aerosol sample analysis.

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  1. Department of Biochemistry and Microbiology, Nelson Mandela Metropolitan University, PO Box 77 000, Port Elizabeth, 6031, South Africa

    Laura Louise Scott, Simoné Downing & Timothy Grant Downing

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  1. Laura Louise Scott
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Correspondence to Timothy Grant Downing.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Scott, L.L., Downing, S. & Downing, T.G. The Evaluation of BMAA Inhalation as a Potential Exposure Route Using a rat Model. Neurotox Res 33, 6–14 (2018). https://doi.org/10.1007/s12640-017-9742-9

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  • DOI: https://doi.org/10.1007/s12640-017-9742-9

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