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Probing the lipid chemistry of neurotoxin-induced hippocampal lesions using multimodal imaging mass spectrometry
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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2014 (English)In: Surface and Interface Analysis, ISSN 0142-2421, E-ISSN 1096-9918, Vol. 46, no 1, 375-378 p.Article in journal (Refereed) Published
Abstract [en]

The environmental toxin -N-methylamino-l-alanine (BMAA) has been causatively linked to neurodegenerative disease pathology. In a rat model, neonatal BMAA resulted in selective uptake in the hippocampal formation and caused learning and memory impairments in adult animals. Moreover, high dose neonatal BMAA exposure resulted in formation of histopathological lesions in the CA1 region of the adult hippocampus; however, the mechanism underlying BMAA induced neuropathology remains elusive. Imaging mass spectrometry (IMS) is a powerful method for spatial interrogation of biochemical distribution in biological tissue with high chemical specificity. The aim of this study was to therefore characterize the lipid microenvironment of BMAA-induced hippocampal lesions in adult rats using matrix-assisted laser desorption/ionization (MALDI) and time-of-flight SIMS (ToF-SIMS imaging). Multimodal imaging was carried out by ToF-SIMS scans of the hippocampal formation followed by whole tissue scans using MALDI imaging. Multivariate analysis was performed on the SIMS data in order to delineate the spatial biochemistry surrounding the lesions. The data show lesion-specific localization of phosphatidylcholine fragments, suggesting neuroinflammatory glial cell activation. Complementary MALDI imaging data showed increased levels of phosphoethanolamines colocalizing with the proteopathic lesions pointing to macroautophagic mechanisms associated with neurotoxin-induced protein accumulation. Multimodal IMS by means of ToF-SIMS and MALDI mass spectrometry proved to be a powerful technique for neurotoxicological research. 

Place, publisher, year, edition, pages
2014. Vol. 46, no 1, 375-378 p.
Keyword [en]
imaging mass spectrometry (IMS), beta-N-methylamino-l-alanine (BMAA), ALS, PD-Complex, matrix-assisted laser desorption, ionization (MALDI), time-of-flight secondary ion mass spectrometry (ToF-SIMS)
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-240448DOI: 10.1002/sia.5418ISI: 000345696200094OAI: oai:DiVA.org:uu-240448DiVA: diva2:776897
19th International Conference on Secondary Ion Mass Spectrometry (SIMS), SEP 29-OCT 04, 2013, Jeju, SOUTH KOREA
Available from: 2015-01-08 Created: 2015-01-07 Last updated: 2015-01-08Bibliographically approved

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Karlsson, OskarBrittebo, Eva B.
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