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2023 (English)In: Journal of the American Society for Mass Spectrometry, ISSN 1044-0305, E-ISSN 1879-1123, Vol. 34, no 5, p. 836-846Article in journal (Refereed) Published
Abstract [en]
The visualization of small metabolites by MALDI mass spectrometry imaging in brain tissue sections is challenging due to low detection sensitivity and high background interference. We present an on-tissue chemical derivatization MALDI mass spectrometry imaging approach for the comprehensive mapping of carboxyls and aldehydes in brain tissue sections. In this approach, the AMPP (1-(4-(aminomethyl)phenyl)pyridin-1-ium chloride) derivatization reagent is used for the covalent charge-tagging of molecules containing carboxylic acid (in the presence of peptide coupling reagents) and aldehydes. This includes free fatty acids and the associated metabolites, fatty aldehydes, dipeptides, neurotoxic reactive aldehydes, amino acids, neurotransmitters and associated metabolites, as well as tricarboxylic acid cycle metabolites. We performed sensitive ultrahigh mass resolution MALDI-MS detection and imaging of various carboxyl-and aldehyde containing endogenous metabolites simultaneously in rodent brain tissue sections. We verified the AMPP-derivatized metabolites by tandem MS for structural elucidation. This approach allowed us to image numerous aldehydes and carboxyls, including certain metabolites which had been undetectable in brain tissue sections. We also demonstrated the application of on-tissue derivatization to carboxyls and aldehydes in coronal brain tissue sections of a nonhuman primate Parkinson's disease model. Our methodology provides a powerful tool for the sensitive, simultaneous spatial molecular imaging of numerous aldehydes and carboxylic acids during pathological states, including neurodegeneration, in brain tissue.
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2023
National Category
Analytical Chemistry Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-502521 (URN)10.1021/jasms.2c00336 (DOI)000972240600001 ()37052344 (PubMedID)
Funder
Swedish Research Council, 2018-03320Swedish Research Council, 2021-03293Swedish Research Council, 2022-04198Swedish Research Council, 2018-05133The Swedish Brain Foundation, FO2021-0318Science for Life Laboratory, SciLifeLab
2023-05-262023-05-262023-05-26Bibliographically approved