文章基本信息

标题：Metabolic profiling of zebrafish (Danio rerio) embryos by NMR spectroscopy reveals multifaceted toxicity of β-methylamino-L-alanine (BMAA)
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作者：Upasana Roy ; Laura Conklin ; Jürgen Schiller 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
页码：17305
DOI：10.1038/s41598-017-17409-8
语种：English
出版社：Springer Nature
摘要：β-methylamino-L-alanine (BMAA) has been linked to several interrelated neurodegenerative diseases. Despite considerable research, specific contributions of BMAA toxicity to neurodegenerative diseases remain to be fully resolved. In the present study, we utilized state-of-the-art high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), applied to intact zebrafish (Danio rerio) embryos, as a model of vertebrate development, to elucidate changes in metabolic profiles associated with BMAA exposure. Complemented by several alternative analytical approaches (i.e., in vivo visualization and in vitro assay), HRMAS NMR identified robust and dose-dependent effect of BMAA on several relevant metabolic pathways suggesting a multifaceted toxicity of BMAA including: (1) localized production of reactive oxygen species (ROS), in the developing brain, consistent with excitotoxicity; (2) decreased protective capacity against excitotoxicity and oxidative stress including reduced taurine and glutathione; (3) inhibition of several developmentally stereotypical energetic and metabolic transitions, i.e., metabolic reprogramming; and (4) inhibition of lipid biosynthetic pathways. Matrix-assisted laser desorption time-of-flight (MALDI-ToF) mass spectrometry further identified specific effects on phospholipids linked to both neural development and neurodegeneration. Taken together, a unified model of the neurodevelopmental toxicity of BMAA in the zebrafish embryo is presented in relation to the potential contribution of BMAA to neurodegenerative disease.