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Cited by 44Mass Spectrometry Techniques and ApplicationsMetabolomics and Mass Spectrometry StudiesSpectroscopy Techniques in Biomedical and Chemical Research

On-Tissue Chemical Derivatization for Comprehensive Mapping of Brain Carboxyl and Aldehyde Metabolites by MALDI-MS Imaging

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Kaya, Ibrahim, Schembri, Luke S., Nilsson, Anna, Shariatgorji, Reza, Baijnath, Sooraj, Zhang, Xiaoqun, Bezard, Erwan, Svenningsson, Per +2 more·2023·Journal of the American Society for Mass Spectrometry
DOI 10.1021/jasms.2c00336PMC PMC10161219
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Abstract

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.

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  • Metabolites that were lower in 4s2M (riboflavin, benzaldehyde, 1-aminocyclopropane-1-carboxylic acid) are not primary intermediates of central carbon metabolism and changes in their abundance may reflect shifts in cofactor handling or dietary metabolite uptake rather than broad changes in core metabolic pathways.

    “Metabolites that were lower in 4s2M - riboflavin, benzaldehyde, and 1-aminocyclopropane-1-carboxylic acid – are not primary intermediates of central carbon metabolism and changes in their abundance may reflect shifts in cofactor handling or dietary metabolite uptake rather than broad changes in core metabolic pathways”

    From Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement (2027) · cites this paper as Kaya et al., 2023

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Authors
Kaya, I., Schembri, L. S., Nilsson, A., Shariatgorji, R., Baijnath, S., Zhang, X., Bezard, E., Svenningsson, P., Odell, L. R., & Andrén, P. E.
Affiliations
  • Uppsala University (SE)
  • Department of Pharmaceutical Biosciences, Spatial Mass Spectrometry, Science for Life Laboratory, Uppsala University, SE-75124 Uppsala, Sweden
  • Karolinska Institutet (SE)
  • Université de Bordeaux, Institut des Maladies Neurodégénératives, F-33000 Bordeaux, France
Corresponding author
  • Odell, Luke R.
  • Andrén, Per E.
ORCID
Venue
Journal of the American Society for Mass Spectrometry
Publisher
American Chemical Society (ACS)
Published
2023-04-13
Volume
34
Issue
5
Pages
836-846
ISSN
  • 1044-0305 (ISSN-L)
  • 1879-1123
DOI
10.1021/jasms.2c00336
PMC
PMC10161219
OpenAlex
W4365442932
Cited by
44
References
2
Citations by year
2026: 17 · 2025: 15 · 2024: 8 · 2023: 4
FWCI
4.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American Society for Mass Spectrometry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Uppsala University Publications (Uppsala University) (submittedVersion, other-oa)
Funders
  • Vetenskapsr?det (2018-05133, 201803320, 201805501, 2021-03293)
  • H2020 Marie Sklodowska-Curie Actions (607517)
  • Stiftelsen f?r?Strategisk Forskning (RIF14-0078)
  • Hj?rnfonden (FO2018-0292)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
Keywords
MALDI mass spectrometry imaging, brain sections, free fatty acids, fatty aldehydes, dipeptides, reactive aldehydes, neurotransmitter metabolites, tricarboxylic acid cycle metabolites, Parkinson's disease model, non-human primate brain, neurodegeneration
MeSH terms
Aldehydes, Amino Acids, Animals, Brain, Carboxylic Acids, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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