ACS Publications. Most Trusted. Most Cited. Most Read
Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Proteome Res. 2025, 24, 3, 1077-1091
    Article

    Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry
    Click to copy article linkArticle link copied!

    Other Access OptionsSupporting Information (2)

    Journal of Proteome Research

    Cite this: J. Proteome Res. 2025, 24, 3, 1077–1091
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jproteome.4c00688
    Published February 8, 2025
    Copyright © 2025 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Lipids are critical to brain structure and function, accounting for approximately 50% of its dry weight. However, the impact of aging on brain lipids remains poorly characterized. To address this, here we applied three complementary mass spectrometry techniques: multiple reaction monitoring (MRM) profiling, untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS), and desorption electrospray ionization-MS imaging (DESI-MSI). We used brains from mice of three age groups: adult (3–4 months), middle-aged (10 months), and old (19–21 months). Phospholipids such as phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol were more abundant, while phosphatidylinositol and phosphatidylserine were reduced in old mice compared to adults or middle-aged mice. Key lipids such as polyunsaturated fatty acids, including DHA, AA, HexCer, SHexCer, and SM, were among the most abundant lipids in aged brains. DESI-MSI revealed spatial lipid distribution patterns consistent with findings from MRM profiling and LC-MS/MS. Integration of lipidomic data with the recently published proteomics data from the same tissues highlighted changes in proteins and phosphorylation levels of several proteins associated with Cer, HexCer, FA, PI, SM, and SHexCer metabolism, aligning with the multiplatform lipid surveillance. These findings shed insight into age-dependent brain lipid changes and their potential contribution to age-related cognitive decline.

    Copyright © 2025 American Chemical Society

    Subjects

    what are subjects

    Keywords

    what are keywords

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jproteome.4c00688.

    • Supplementary Tables. Table S1: MRMs identified in the aging brain by MRM profiling. Table S2: MRMs significantly changing in the aging brain. Table S3: Lipids detected by Untargeted LC-MS/MS in the positive ion mode (annotated by MSP Spectral database) Table S4: Lipids detected by Untargeted LC-MS/MS in the positive ion mode (annotated by the mass spectral atlas) Table S5: Lipids detected by Untargeted LC-MS/MS in the negative ion mode (annotated by MSP Spectral database) Table S6: Lipids detected by Untargeted LC-MS/MS in the negative ion mode (annotated by the mass spectral atlas) Table S7: Multiple Sample Test results for lipids identified in the untargeted LC-MS/MS positive ion mode. Table S8: Multiple Sample Test results for lipids identified in the untargeted LC-MS/MS negative ion mode. Table S9: Lipids identified in the untargeted LC-MS/MS analyzes that were significantly changing in the brain. Table S10: Lipid–protein pathway mapping. Table S11: Clusters identified in the DESI MSI (−ve) segmentation and their respective ion intensities. Table S12: Annotated DESI MSI identified lipids (XLSX)

    • Supplementary Figures. Figure S1. Lipids detected in untargeted LC-MS/MS analysis. Figure S2. Volcano plots of changes in lipids in the aged mouse brain compared to adults. Figure S3. Representative DESI-MSI spectra. Figure S4. Notable lipids of gray and white matter identified in the DESI MSI analysis in positive negative-ion mode. Figure S5: Examples of phospholipids identified in more than one analysis. Figure S6: PE(P-36:2), a plasmalogen identified in all three analyses. Figure S7: Heat map of proteins significantly changing from proteomics data mapped from the lipidomics data in the brain of aging mice. Figure S8. Pathway mapping of lipids and integration with previously published proteomics data in aging mice (DOCX)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article has not yet been cited by other publications.

    Download PDF
    Go to Journal of Proteome Research
    Get e-Alerts
    Get e-Alerts

    Journal of Proteome Research

    Cite this: J. Proteome Res. 2025, 24, 3, 1077–1091
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jproteome.4c00688
    Published February 8, 2025
    Copyright © 2025 American Chemical Society
    Request reuse permissions

    Article Views

    353

    Altmetric

    -

    Citations

    -
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.