MALDI imaging delineates hippocampal glycosphingolipid changes associated with neurotoxin induced proteopathy following neonatal BMAA exposure
Journal article, 2017

The environmental toxin S-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 (460 mg/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 460 mg/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 sloop 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. (

Environmental toxin

Imaging mass spectrometry

Protein

Beta-N-methylamino-L-alanine (BMAA)

Author

Oskar Karlsson

Harvard School of Public Health

Uppsala University

Karolinska Institutet

W. Michno

University of Gothenburg

Y. Ransome

Harvard School of Public Health

Jörg Hanrieder

University of Gothenburg

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Analytical Chemistry

Biochimica et Biophysica Acta - Proteins and Proteomics

1570-9639 (ISSN)

Vol. 1865 7 740-746

Subject Categories

Biochemistry and Molecular Biology

Environmental Sciences

DOI

10.1016/j.bbapap.2016.12.004

More information

Latest update

11/22/2019