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MALDI imaging delineates hippocampal glycosphingolipid changes associated with
neurotoxin induced proteopathy following neonatal BMAA exposure
#MMPMID27956354
Karlsson O
; Michno W
; Ransome Y
; Hanrieder J
Biochim Biophys Acta Proteins Proteom
2017[Jul]; 1865
(7
): 740-746
PMID27956354
show ga
The environmental toxin ?-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 S100? 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.
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