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MALDI imaging delineates hippocampal glycosphingolipid changes associated with neurotoxin induced proteopathy following neonatal BMAA exposure.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, Sweden; Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, USA.
2017 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1865, no 7, 740-746 p.Article in journal (Refereed) Published
Abstract [en]

The environmental toxin β-N-methylamino-L-alanine (BMAA) has been proposed to contribute to neurodegenerative diseases. We have previously shown that neonatal exposure to BMAA results in dose-dependent cognitive impairments, proteomic alterations and progressive neurodegeneration in the hippocampus of adult rats. A high BMAA dose (460mg/kg) also induced intracellular fibril formation, increased protein ubiquitination and enrichment of proteins important for lipid transport and metabolism. The aim of this study was therefore to elucidate the role of neuronal lipids in BMAA-induced neurodegeneration. By using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), we characterized the spatial lipid profile in the hippocampus of six month-old rats that were treated neonatally (postnatal days 9-10) with 460mg/kg BMAA. Multivariate statistical analysis revealed long-term changes in distinct ganglioside species (GM, GD, GT) in the dentate gyrus. These changes could be a consequence of direct effects on ganglioside biosynthesis through the b-series (GM3-GD3-GD2-GD1b-GT1b) and may be linked to astrogliosis. Complementary immunohistochemistry experiments towards GFAP and S100β further verified the role of increased astrocyte activity in BMAA-induced brain damage. This highlights the potential of imaging MS for probing chemical changes associated with neuropathological mechanisms in situ. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Place, publisher, year, edition, pages
2017. Vol. 1865, no 7, 740-746 p.
Keyword [en]
Beta-N-methylamino-L-alanine (BMAA), Environmental toxin, Gliosis, Glycosphingolipids, Imaging mass spectrometry, Protein pathology
National Category
Pharmacology and Toxicology Medicinal Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-321815DOI: 10.1016/j.bbapap.2016.12.004ISI: 000404825500002PubMedID: 27956354OAI: oai:DiVA.org:uu-321815DiVA: diva2:1094898
Funder
Swedish Research Council, 2014-6447Swedish Research Council FormasCarl Tryggers foundation The Dementia Association - The National Association for the Rights of the DementedStiftelsen Gamla Tjänarinnor
Available from: 2017-05-11 Created: 2017-05-11 Last updated: 2017-10-09Bibliographically approved

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