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The Effects of Long-term, Low-dose β-N-methylamino-l-alanine (BMAA) Exposures in Adult SODG93R Transgenic Zebrafish

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A Correction to this article was published on 24 August 2023

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Abstract

β-N-Methylamino-l-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease. We used a transgenic zebrafish with an ALS-associated mutation, compared with wild-type fish to explore the potential neurotoxic effects of BMAA through chronic long-term exposures. While our results revealed low concentrations of BMAA in the brains of exposed fish, we found no evidence of decreased swim performance or behavioral differences that might be reflective of neurodegenerative disease. Further research is needed to determine if chronic BMAA exposure in adult zebrafish is a suitable model to study neurodegenerative disease initiation and/or progression.

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Acknowledgements

We are grateful to the late Dr. Christine Beattie of Ohio State University for the gift of the sodG93R transgenic zebrafish. Brain Chemistry Labs thanks the William C. and Joyce C. O’Neil Charitable Trust for support of this research. We thank members of the Planchart lab for helpful discussions during the execution of this work. We dedicate this work to the memory of Dr. Michael Bereman, who bravely fought ALS for 6 years and provided us with the inspiration for this work.

Funding

Ryan Weeks was supported by a Ruth L. Kirschstein National Research Service Award Institutional Training Grant (T32 ES007046); this work was supported in part by the Center for Human Health and the Environment (P30ES025128); funding for AP provided by N.C. State University. Paul Cox lab: William C. and Joyce C. O’Neil Charitable Trust.

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Authors and Affiliations

  1. Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA

    Ryan D. Weeks, Shaunacee Howell, Preethi Thunga, Adrian J. Green & Antonio Planchart

  2. Brain Chemistry Labs, Institute for Ethnomedicine, Box 3464, Jackson, WY, 83001, USA

    Sandra A. Banack, James S. Metcalf & Paul A. Cox

  3. Program in Toxicology, North Carolina State University, Raleigh, NC, 27695, USA

    Ryan D. Weeks, Adrian J. Green & Antonio Planchart

  4. Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA

    Ryan D. Weeks, Adrian J. Green & Antonio Planchart

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  1. Ryan D. Weeks
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  3. Shaunacee Howell
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  8. Antonio Planchart
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Contributions

Ryan Weeks: primary researcher responsible for planning and conducting experiments, along with fish husbandry; assisted with mass spectrometry sample preparation. Sandra Banack: conducted all mass spectrometry experiments and analysis. Shaunacee Howell: aided in conducting behavioral experiments and fish husbandry. Preethi Thunga: responsible for swim tunnel data statistical analysis. Adrian Green: aided in experimental design and behavioral assays, responsible for light/dark assay data analysis. Paul Cox: collaborating PI who advised and directed mass spectrometry experiments. Antonio Planchart: primary PI responsible for project, including mentoring, experimental design, data analysis, and major funding.

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Correspondence to Antonio Planchart.

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All fish husbandry, anesthesia, and euthanasia were conducted in accordance with NC State Institutional Animal Care and Use Committee (IACUC)-approved protocols.

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Weeks, R.D., Banack, S.A., Howell, S. et al. The Effects of Long-term, Low-dose β-N-methylamino-l-alanine (BMAA) Exposures in Adult SODG93R Transgenic Zebrafish. Neurotox Res 41, 481–495 (2023). https://doi.org/10.1007/s12640-023-00658-z

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