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Environmental neurotoxin interaction with proteins: Dose-dependent increase of free and protein-associated BMAA (beta-N-methylamino-L-alanine) in neonatal rat brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Stockholm Univ, Dept Environm Sci & Analyt Chem, SE-10691 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 15570Article in journal (Refereed) Published
Abstract [en]

beta-Methylamino-L-alanine (BMAA) is implicated in the aetiology of neurodegenerative disorders. Neonatal exposure to BMAA induces cognitive impairments and progressive neurodegenerative changes including intracellular fibril formation in the hippocampus of adult rats. It is unclear why the neonatal hippocampus is especially vulnerable and the critical cellular perturbations preceding BMAA-induced toxicity remains to be elucidated. The aim of this study was to compare the level of free and protein-associated BMAA in neonatal rat brain and peripheral tissues after different exposures to BMAA. Ultra-high performance liquid chromatography-tandem mass spectrometry analysis revealed that BMAA passed the neonatal blood-brain barrier and was distributed to all studied brain areas. BMAA was also associated to proteins in the brain, especially in the hippocampus. The level in the brain was, however, considerably lower compared to the liver that is not a target organ for BMAA. In contrast to the liver there was a significantly increased level of protein-association of BMAA in the hippocampus and other brain areas following repeated administration suggesting that the degradation of BMAA-associated proteins may be lower in neonatal brain than in the liver. Additional evidence is needed in support of a role for protein misincorporation in the neonatal hippocampus for long-term effects of BMAA.

Place, publisher, year, edition, pages
2015. Vol. 5, 15570
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-267198DOI: 10.1038/srep15570ISI: 000363397500001PubMedID: 26498001OAI: oai:DiVA.org:uu-267198DiVA: diva2:872525
Funder
Swedish Research Council Formas
Available from: 2015-11-19 Created: 2015-11-19 Last updated: 2017-12-01Bibliographically approved

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