The detection of glycosphingolipids in brain tissue sections by imaging mass spectrometry using gold nanoparticles

  • Naoko Goto-Inoue
  • Takahiro Hayasaka
  • Nobuhiro Zaima
  • Yukiyasu Kashiwagi
  • Mari Yamamoto
  • Masami Nakamoto
  • Mitsutoshi Setou
Application Note


Glycosphingolipids (GSLs) are amphiphilic molecules consisting of a hydrophilic carbohydrate chain and a hydrophobic ceramide moiety. They appear to be involved primarily in biological processes such as cell proliferation, differentiation, and signaling. To investigate the mechanism of brain function in more detail, a more highly sensitive method that would reveal the GSL distribution in the brain is required. In this report, we describe a simple and efficient method for mapping the distribution and localization of GSLs present in mouse brain sections using nanoparticle-assisted laser desorption/ionization imaging mass spectrometry (IMS). We have developed and tested gold nanoparticles (AuNPs) as a new matrix to maximize the detection of GSLs. A matrix of AuNPs modified with alkylamine was used to detect various GSLs, such as minor molecular species of sulfatides and gangliosides, in mouse brain sections; these GSLs were hardly detected using 2,5-dihydroxybenzoic acid (DHB), which is the conventional matrix for GSLs. We achieved approximately 20 times more sensitive detection of GSLs using AuNPs compared to a DHB matrix. We believe that our new approach using AuNPs in IMS could lead to a new strategy for analyzing basic biological mechanisms and several diseases through the distribution of minor GSLs.


Image Mass Spectrometric MALDI Mass Spectrometry Brain Tissue Section Image Mass Spectrometric Conventional Matrix 
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  1. 1.
    Hannun, Y. A.; Bell, R. M. Functions of Sphingolipids and Sphingolipid Breakdown Products in Cellular Regulation. Science 1989, 243(4890), 500–507.CrossRefGoogle Scholar
  2. 2.
    Hakomori, S.; Handa, K.; Iwabuchi, K.; Yamamura, S.; Prinetti, A. New Insights in Glycosphingolipid Function: “Glycosignaling Domain,” a Cell Surface Assembly of Glycosphingolipids with Signal Transducer Molecules, Involved in Cell Adhesion Coupled with Signaling. Glycobiology 1998, 8(10), xi-xix.CrossRefGoogle Scholar
  3. 3.
    Sugiura, Y.; Shimma, S.; Konishi, Y.; Yamada, M. K.; Setou, M. Imaging Mass Spectrometry Technology and Application on Ganglioside Study; Visualization of Age-Dependent Accumulation of C20-Ganglioside Molecular Species in the Mouse Hippocampus. PLoS One 2008, 3(9), e3232.CrossRefGoogle Scholar
  4. 4.
    Chan, K.; Lanthier, P.; Liu, X.; Sandhu, J. K.; Stanimirovic, D.; Li, J. MALDI Mass Spectrometry Imaging of Gangliosides in Mouse Brain Using Ionic Liquid Matrix. Anal. Chim. Acta 2009, 639(1–2), 57–61.CrossRefGoogle Scholar
  5. 5.
    Colsch, B.; Woods, A. S. Localization and Imaging of Sialylated Glycosphingolipids in Brain Tissue Sections by MALDI Mass Spectrometry. Glycobiology 2010, 20(6), 661–667.CrossRefGoogle Scholar
  6. 6.
    Zaima, N.; Hayasaka, T.; Goto-Inoue, N.; Setou, M. Imaging of Metabolites by MALDI Mass Spectrometry. J. Oleo. Sci. 2009, 58(8), 415–419.CrossRefGoogle Scholar
  7. 7.
    Shimma, S.; Sugiura, Y.; Hayasaka, T.; Zaima, N.; Matsumoto, M.; Setou, M. Mass Imaging and Identification of Biomolecules with MALDI-QIT-TOF-Based System. Anal. Chem. 2008, 80(3), 878–885.CrossRefGoogle Scholar
  8. 8.
    Hayasaka, T.; Goto-Inoue, N.; Zaima, N.; Kimura, Y.; Setou, M. Organ-Specific Distributions of Lysophosphatidylcholine and Triacylglycerol in Mouse Embryo. Lipids 2009, 44(9), 837–848.CrossRefGoogle Scholar
  9. 9.
    Andersson, M.; Groseclose, M. R.; Deutch, A. Y.; Caprioli, R. M. Imaging Mass Spectrometry of Proteins and Peptides: 3D Volume Reconstruction. Nat. Methods 2008, 5(1), 101–108.CrossRefGoogle Scholar
  10. 10.
    Groseclose, M. R.; Andersson, M.; Hardesty, W. M.; Caprioli, R. M. Identification of Proteins Directly from Tissue: In Situ Tryptic Digestions Coupled with Imaging Mass Spectrometry. J. Mass Spectrom. 2007, 42(2), 254–262.CrossRefGoogle Scholar
  11. 11.
    Shimma, S.; Sugiura, Y.; Hayasaka, T.; Hoshikawa, Y.; Noda, T.; Setou, M. MALDI-Based Imaging Mass Spectrometry Revealed Abnormal Distribution of Phospholipids in Colon Cancer Liver Metastasis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2007, 855(1), 98–103.CrossRefGoogle Scholar
  12. 12.
    Wen, X.; Dagan, S.; Wysocki, V. H. Small-Molecule Analysis with Silicon-Nanoparticle-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 2007, 79(2), 434–444.CrossRefGoogle Scholar
  13. 13.
    Wu, H. P.; Yu, C. J.; Lin, C. Y.; Lin, Y. H.; Tseng, W. L. Gold Nanoparticles as Assisted Matrices for the Detection of Biomolecules in a High-Salt Solution through Laser Desorption/Ionization Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2009, 20(5), 875–882.CrossRefGoogle Scholar
  14. 14.
    Chiu, T. C.; Chang, L. C.; Chiang, C. K.; Chang, H. T. Determining Estrogens Using Surface-Assisted Laser Desorption/Ionization Mass Spectrometry with Silver Nanoparticles as the Matrix. J. Am. Soc. Mass Spectrom. 2008, 19(9), 1343–1346.CrossRefGoogle Scholar
  15. 15.
    Sherrod, S. D.; Diaz, A. J.; Russell, W. K.; Cremer, P. S.; Russell, D. H. Silver Nanoparticles as Selective Ionization Probes for Analysis of Olefins by Mass Spectrometry. Anal. Chem. 2008, 80(17), 6796–6799.CrossRefGoogle Scholar
  16. 16.
    Taira, S.; Sugiura, Y.; Moritake, S.; Shimma, S.; Ichiyanagi, Y.; Setou, M. Nanoparticle-Assisted Laser Desorption/Ionization Based Mass Imaging with Cellular Resolution. Anal. Chem. 2008, 80(12), 4761–4766.CrossRefGoogle Scholar
  17. 17.
    Ageta, H.; Asai, S.; Sugiura, Y.; Goto-Inoue, N.; Zaima, N.; Setou, M. Layer-Specific Sulfatide Localization in Rat Hippocampus Middle Molecular Layer is Revealed by Nanoparticle-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry. Med. Mol. Morphol. 2009, 42(1), 16–23.CrossRefGoogle Scholar
  18. 18.
    Jackson, S. N.; Ugarov, M.; Egan, T.; Post, J. D.; Langlais, D.; Albert Schultz, J.; Woods, A. S. MALDI-Ion Mobility-TOFMS Imaging of Lipids in Rat Brain Tissue. J. Mass Spectrom. 2007, 42(8), 1093–1098.CrossRefGoogle Scholar
  19. 19.
    Yamamoto, M.; Kashiwagi, Y.; Nakamoto, M. Size-Controlled Synthesis of Gold Nanoparticles by Thermolysis of a Gold(I)-Sulfide Complex in the Presence of Alkylamines. Z Naturforsch. B 2009, 64(11–12), 1305–1311.Google Scholar
  20. 20.
    Jackson, S. N.; Wang, H. Y. J.; Woods, A. S. Direct Profiling of Lipid Distribution in Brain Tissue Using MALDI-TOFMS. Anal. Chem. 2005, 77(14), 4523–4527.CrossRefGoogle Scholar
  21. 21.
    Harvey, D. J. Analysis of Carbohydrates and Glycoconjugates by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry: An Update Covering the Period 1999–2000. Mass Spectrom. Rev. 2006, 25(4), 595–662.CrossRefGoogle Scholar
  22. 22.
    Costello, C. E.; Juhasz, P.; Perreault, H. New Mass Spectral Approaches to Ganglioside Structure Determinations. Prog. Brain Res. 1994, 101, 45–61.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2010

Authors and Affiliations

  • Naoko Goto-Inoue
    • 1
  • Takahiro Hayasaka
    • 1
  • Nobuhiro Zaima
    • 1
  • Yukiyasu Kashiwagi
    • 1
  • Mari Yamamoto
    • 2
  • Masami Nakamoto
    • 2
  • Mitsutoshi Setou
    • 1
  1. 1.Department of Molecular Anatomy, Molecular Imaging Frontier Research CenterHamamatsu University School of MedicineShizuokaJapan
  2. 2.Osaka Municipal Technical Research InstituteOsakaJapan

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