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Layer-specific sulfatide localization in rat hippocampus middle molecular layer is revealed by nanoparticle-assisted laser desorption/ionization imaging mass spectrometry

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Abstract

Lipids are major structural component of the brain and play key roles in signaling functions in the central nervous system (CNS), such as the hippocampus. In particular, sulfatide is an abundant glycosphingolipid component of both the central and the peripheral nervous system and is an essential lipid component of myelin membranes. Lack of sulfatide is observed in myelin deformation and neurological deficits. Previous studies with antisulfatide antibody have investigated distribution of sulfatide expression in neurons; however, this method cannot distinguish the differences of sulfatide lipid species raised by difference of carbon-chain length in the ceramide portion in addition to the differences of sulfatide and seminolipid. In this study, we solved the problem by our recently developed nanoparticle-assisted laser desorption/ionization (nano-PALDI)-based imaging mass spectrometry (IMS). We revealed that the level of sulfatide in the middle molecular layer was significantly higher than that in granule cell layers and the inner molecular layer in the dentate gyrus of rat hippocampus.

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References

  1. Kakela R, Somerharju P, Tyynela J (2003) Analysis of phospholipid molecular species in brains from patients with infantile and juvenile neuronal-ceroid lipofuscinosis using liquid chromatography-electrospray ionization mass spectrometry. J Neurochem 84:1051–1065

    Article  PubMed  CAS  Google Scholar 

  2. He X, Chen F, McGovern MM, Schuchman EH (2002) A fluorescence-based, high-throughput sphingomyelin assay for the analysis of Niemann-Pick disease and other disorders of sphingomyelin metabolism. Anal Biochem 306:115–123

    Article  PubMed  CAS  Google Scholar 

  3. Han XDMH, McKeel DW Jr, Kelley J, Morris JC (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer’s disease: potential role in disease pathogenesis. J Neurochem 82:809–818

    Article  PubMed  CAS  Google Scholar 

  4. Irizarry MC (2003) A turn of the sulfatide in Alzheimer’s disease. Ann Neurol 54:7–8

    Article  PubMed  Google Scholar 

  5. Bosio A, Binczek E, Haupt WF, Stoffel W (1998) Composition and biophysical properties of myelin lipid define the neurological defects in galactocerebroside- and sulfatide-deficient mice. J Neurochem 70:308–315

    Article  PubMed  CAS  Google Scholar 

  6. Norton WT, Cammer W (1984) Isolation and characterization of myelin. Plenum Press, New York, pp 147–195

    Google Scholar 

  7. Ishibashi T, Dupree JL, Ikenaka K, Hirahara Y, Honke K, Peles E, Popko B, Suzuki K, Nishino H, Baba H (2002) A myelin galactolipid, sulfatide, is essential for maintenance of ion channels on myelinated axon but not essential for initial cluster formation. J Neurosci 22:6507–6514

    PubMed  CAS  Google Scholar 

  8. Vos JP, Lopes-Cardozo M, Gadella BM (1994) Metabolic and functional aspects of sulfogalactolipids. Biochim Biophys Acta 1211:125–149

    PubMed  CAS  Google Scholar 

  9. Ishizuka I (1997) Chemistry and functional distribution of sulfoglycolipids. Prog Lipid Res 36:245–319

    Article  PubMed  CAS  Google Scholar 

  10. Marbois BN, Faull KF, Fluharty AL, Raval-Fernandes S, Rome LH (2000) Analysis of sulfatide from rat cerebellum and multiple sclerosis white matter by negative ion electrospray mass spectrometry. Biochim Biophys Acta 1484:59–70

    PubMed  CAS  Google Scholar 

  11. Marcus J, Honigbaum S, Shroff S, Honke K, Rosenbluth J, Dupree JL (2006) Sulfatide is essential for the maintenance of CNS myelin and axon structure. Glia 53:372–381

    Article  PubMed  CAS  Google Scholar 

  12. Latov N (1995) Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies. Ann Neurol 37(suppl 1): S32–S42

    Article  PubMed  Google Scholar 

  13. von Figura K, Gieselmann V, Jaeken J (2001) Metachromatic leukodystrophy. McGraw-Hill, New York

    Google Scholar 

  14. Krivit W (2004) Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol 26:119–132

    Article  PubMed  Google Scholar 

  15. Pernber Z, Molander-Melin M, Berthold CH, Hansson E, Fredman P (2002) Expression of the myelin and oligodendrocyte progenitor marker sulfatide in neurons and astrocytes of adult rat brain. J Neurosci Res 69:86–93

    Article  PubMed  CAS  Google Scholar 

  16. Bansal R, Warrington AE, Gard AL, Ranscht B, Pfeiffer SE (1989) Multiple and novel specificities of monoclonal antibodies O1, O4, and R-mAb used in the analysis of oligodendrocyte development. J Neurosci Res 24:548–557

    Article  PubMed  CAS  Google Scholar 

  17. Saga K (2005) Application of cryofixation and cryoultramicrotomy for biological electron microscopy. Med Mol Morphol 38:155–160

    Article  PubMed  Google Scholar 

  18. Setou M, Danev R, Atsuzawa K, Yao I, Fukuda Y, Usuda N, Nagayama K (2006) Mammalian cell nano structures visualized by cryo Hilbert differential contrast transmission electron microscopy. Med Mol Morphol 39:176–180

    Article  PubMed  Google Scholar 

  19. Nakagawa T, Setou M, Seog DH, Ogasawara K, Dohmae N, Takio K, Hirokawa N (2000) A novel motor, KIF13A, transports mannose-6-phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell 103:569–581

    Article  PubMed  CAS  Google Scholar 

  20. Ikegami K, Heier RL, Taruishi M, Takagi H, Mukai M, Shimma S, Taira S, Hatanaka K, Morone N, Yao I, et al (2007) Loss of alpha-tubulin polyglutamylation in ROSA22 mice is associated with abnormal targeting of KIF1A and modulated synaptic function. Proc Natl Acad Sci U S A 104:3213–3218

    Article  PubMed  CAS  Google Scholar 

  21. Ikegami K, Horigome D, Mukai M, Livnat I, Macgregor GR, Setou M (2008) TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1. FEBS Lett 582:1129–1134

    Article  PubMed  CAS  Google Scholar 

  22. Shimma S, Setou M (2005) Review of imaging mass spectrometry. J Mass Spectrom Soc Jpn 53:230–238

    CAS  Google Scholar 

  23. Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7:493–496

    Article  PubMed  CAS  Google Scholar 

  24. Chaurand P, Rahman MA, Hunt T, Mobley JA, Gu G, Latham JC, et al. (2008) Monitoring mouse prostate development by profiling and imaging mass spectrometry. Mol Cell Proteomics 7:411–423

    PubMed  CAS  Google Scholar 

  25. Burnum KE, Tranguch S, Mi D, Daikoku T, Dey SK, Caprioli RM (2008) Imaging mass spectrometry reveals unique protein profiles during embryo implantation. Endocrinology 149:3274–3278

    Article  PubMed  CAS  Google Scholar 

  26. Luxembourg SL, Mize TH, McDonnell LA, Heeren RM (2004) High-spatial resolution mass spectrometric imaging of peptide and protein distributions on a surface. Anal Chem 76:5339–5344

    Article  PubMed  CAS  Google Scholar 

  27. Cornett DS, Frappier SL, Caprioli RM (2008) MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal Chem 80:5648–5653

    Article  PubMed  CAS  Google Scholar 

  28. Garrett TJ, Yost RA (2006) Analysis of intact tissue by intermediate-pressure MALDI on a linear ion trap mass spectrometer. Anal Chem 78:2465–2469

    Article  PubMed  CAS  Google Scholar 

  29. Rohner TC, Staab D, Stoeckli M (2005) MALDI mass spectrometric imaging of biological tissue sections. Mech Ageing Dev 126: 177–185

    Article  PubMed  CAS  Google Scholar 

  30. Shimma S, Setou M (2007) Mass microscopy to reveal distinct localization of heme B (m/z 616) in colon cancer liver metastasis. J Mass Spectrom Soc Jpn 55:145–148

    CAS  Google Scholar 

  31. Shimma S, Sugiura Y, Hayasaka T, Hoshikawa Y, Noda T, et al (2007) MALDI-based imaging mass spectrometry revealed abnormal distribution of phospholipids in colon cancer liver metastasis. J Chromatogr B Anal Technol Biomed Life Sci 855:98–103

    Article  CAS  Google Scholar 

  32. Shimma S, Sugiura Y, Hayasaka T, Zaima N, Matsumoto M, et al (2008) Mass imaging and identification of biomolecules with MALDI-QIT-TOF-based system. Anal Chem 80:878–885

    Article  PubMed  CAS  Google Scholar 

  33. Sugiura Y, Shimma S, Setou M (2006) Two-step matrix application technique to improve ionization efficiency for matrix-assisted laser desorption/ionization in imaging mass spectrometry. Anal Chem 78:8227–8235

    Article  PubMed  CAS  Google Scholar 

  34. Sugiura Y, Shimma S, Setou M (2006) Thin sectioning improves the peak intensity and signal-to-noise ratio in direct tissue mass spectrometry. J Mass Spectrom Soc Jpn 54:45–48

    CAS  Google Scholar 

  35. Yao I, Sugiura Y, Matsumoto M, Setou M (2008) In situ proteomics with imaging mass spectrometry and principal component analysis in the Scrapper-knockout mouse brain. Proteomics 8:3692–3701

    Article  PubMed  CAS  Google Scholar 

  36. Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M (2008) 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 3:e3232

    Article  PubMed  CAS  Google Scholar 

  37. Hosokawa N, Sugiura Y, Setou M (2008) Spectrum normalization method using an external standard in mass spectrometric imaging. J Mass Spectrom Soc Jpn 56:77–81

    CAS  Google Scholar 

  38. Hayasaka T, Goto-Inoue N, Sugiura Y, Zaima N, Nakanishi H, Ohishi K, et al. (2008) Matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry reveals a layered distribution of phospholipid molecular species in the mouse retina. Rapid Commun Mass Spectrom 22:1–12

    Article  CAS  Google Scholar 

  39. Taira S, Sugiura Y, Moritake S, Shimma S, Ichiyanagi Y, Setou M (2008) Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution. Anal Chem 80:4761–4766

    Article  PubMed  CAS  Google Scholar 

  40. Lanza GM, Abendschein DR, Hall CH, et al. (2000) In vivo molecular imaging of stretch-induced tissue factor in carotid arteries with ligand-targeted nanoparticles. J Am Soc Echocardiogr 13:608–614

    Article  PubMed  CAS  Google Scholar 

  41. Moritake S, Song SY, Hatanaka T, Yuasa S, Setou M (2007) Functionalized nano-magnetic particles for an in vivo delivery system. J Nanosci Nanotechnol 7:937–944

    Article  PubMed  CAS  Google Scholar 

  42. Paxinos G (1995) The rat nervous system, 2nd edn. Academic Press, Sydney

    Google Scholar 

  43. Shepherd GM (1997) The synaptic organization of the brain, 4th edn. Oxford University Press, New York

    Google Scholar 

  44. Jackson SN, Wang HY, Woods AS (2007) In situ structural characterization of glycerophospholipids and sulfatides in brain tissue using MALDI-MS/MS. J Am Soc Mass Spectrom 18:17–26

    Article  PubMed  CAS  Google Scholar 

  45. Ikeda K, Shimizu T, Taguchi R (2008) Targeted analysis of ganglioside and sulfatide molecular species by LC/ESI-MS/MS with theoretically expanded multiple reaction monitoring. J Lipid Res 49:2678–2689

    Article  PubMed  CAS  Google Scholar 

  46. Harvey DJ (1999) Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates. Mass Spectrom Rev 18:349–450

    Article  PubMed  CAS  Google Scholar 

  47. Jackson SN, Wang HY, Woods AS (2005) Direct profiling of lipid distribution in brain tissue using MALDI-TOFMS. Anal Chem 77:4523–4527

    Article  PubMed  CAS  Google Scholar 

  48. Han X, Gross RW (2001) Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal Biochem 295:88–100

    Article  PubMed  CAS  Google Scholar 

  49. Hsu FF, Turk J (2001) Structural determination of glycosphingolipids as lithiated adducts by electrospray ionization mass spectrometry using low-energy collisional-activated dissociation on a triple stage quadrupole instrument. J Am Soc Mass Spectrom 12:61–79

    Article  PubMed  CAS  Google Scholar 

  50. Molander-Melin M, Pernber Z, Franken S, Gieselmann V, Mansson JE, Fredman P (2004) Accumulation of sulfatide in neuronal and glial cells of arylsulfatase A deficient mice. J Neurocytol 33:417–427

    PubMed  CAS  Google Scholar 

  51. Hjorth-Simonsen A (1972) Projection of the lateral part of the entorhinal area to the hippocampus and fascia dentata. J Comp Neurol 146:219–232

    Article  PubMed  CAS  Google Scholar 

  52. Laurberg S, Sorensen KE (1981) Associational and commissural collaterals of neurons in the hippocampal formation (hilus fasciae dentatae and subfield CA3). Brain Res 212:287–300

    Article  PubMed  CAS  Google Scholar 

  53. Frotscher M, Jonas P, Sloviter RS (1981) Synapses formed by normal and abnormal hippocampal mossy fibers. Cell Tissue Res 326:361–367

    Article  Google Scholar 

  54. Coetzee T, Fujita N, Dupree J, Shi R, Blight A, Suzuki K, Suzuki K, Popko B (1996) Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86:209–219

    Article  PubMed  CAS  Google Scholar 

  55. Honke K, Hirahara Y, Dupree J, Suzuki K, Popko B, Fukushima K, Fukushima J, Nagasawa T, Yoshida N, Wada Y, Taniguchi N (2002) Paranodal junction formation and spermatogenesis require sulfoglycolipids. Proc Natl Acad Sci U S A 99: 4227–4232

    Article  PubMed  CAS  Google Scholar 

  56. Ramakrishnan H, Hedayati KH, Lüllmann-Rauch R, Wessig C, Fewou SN, Maier H, Goebel H-H, Gieselmann V, Eckhardt M (2007) Increasing sulfatide synthesis in myelin-forming cells of arylsulfatase A-deficient mice causes demyelination and neurological symptoms reminiscent of human metachromatic leukodystrophy. J Neurosci 27:9482–9490

    Article  PubMed  CAS  Google Scholar 

  57. Jungalwala FB (1974) Synthesis and turnover of cerebroside sulfate of myelin in adult and developing rat brain. J Lipid Res 15: 114–123

    PubMed  CAS  Google Scholar 

  58. Schulte S, Stoffel W (1993) Ceramide UDP galactosyltransferase from myelinating rat brain: purification, cloning, and expression. Proc Natl Acad Sci U S A 90:10265–10269

    Article  PubMed  CAS  Google Scholar 

  59. Honke K, Yamane M, Ishii A, Kobayashi T, Makita A (1996) Purification and characterization of 3′-phosphoadenosine-5′-phosphosulfate: GalCer sulfotransferase from human renal cancer cells. J Biochem 119:421–427

    PubMed  CAS  Google Scholar 

  60. Honke K, Tsuda M, Hirahara Y, Ishii A, Makita A, Wada Y (1997) Molecular cloning and expression of cDNA encoding human 3′-phosphoadenylylsulfate:galactosylceramide 3′-sulfotransferase. J Biol Chem 272:4864–4868

    Article  PubMed  CAS  Google Scholar 

  61. Tadano-Aritomi K, Matsuda J, Fujimoto H, Suzuki K, Ishizuka I (2003) Seminolipid and its precursor/degradative product, galactosylalkylacylglycerol, in the testis of saposin A- and prosaposindeficient mice. J Lipid Res 44:1737–1743

    Article  PubMed  CAS  Google Scholar 

  62. Neufeld EF (1991) Lysosomal storage diseases. Annu Rev Biochem 60:257–280

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Mitsubishi Kagaku Institute of Life Sciences (MITILS), Tokyo, Japan

    Hiroshi Ageta, Sayaka Asai, Yuki Sugiura, Nobuhiro Zaima & Mitsutoshi Setou

  2. Department of Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka, 431-3192, Japan

    Yuki Sugiura, Naoko Goto-Inoue, Nobuhiro Zaima & Mitsutoshi Setou

  3. Department of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa, Japan

    Yuki Sugiura

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  1. Hiroshi Ageta
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  2. Sayaka Asai
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  3. Yuki Sugiura
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  4. Naoko Goto-Inoue
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  5. Nobuhiro Zaima
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  6. Mitsutoshi Setou
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Correspondence to Mitsutoshi Setou.

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H. Ageta and S. Asai contributed equally to this work.

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Ageta, H., Asai, S., Sugiura, Y. et al. Layer-specific sulfatide localization in rat hippocampus middle molecular layer is revealed by nanoparticle-assisted laser desorption/ionization imaging mass spectrometry. Med Mol Morphol 42, 16–23 (2009). https://doi.org/10.1007/s00795-008-0427-6

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