Methods for Human Olfactory Bulb Tissue Studies Using Peptide/Protein MALDI-TOF Imaging Mass Spectrometry (MALDI-IMS)

  • Ibon Iloro
  • Joaquín Fernández-Irigoyen
  • Iraide Escobes
  • Mikel Azkargorta
  • Enrique Santamaría
  • Felix Elortza
Protocol
Part of the Neuromethods book series (NM, volume 127)

Abstract

The olfactory bulb (OB) is the first site for the processing of olfactory information in the brain, and its deregulation is one of the earliest features of neurodegenerative diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques for characterization of the OB functionality. However, little attention has been given to the specific molecular landscape of the OB from the perspective of proteomics. Recently, the imaging mass spectrometry (IMS) using matrix-assisted laser desorption/ionization (MALDI) has emerged as a powerful tool for analyzing the spatial distribution of peptides and small proteins (among other molecules) within the tissues. The obtained signals can be correlated with underlying tissue architecture without any geometrical distortion, enabling the study of the functional molecules within tissues, i.e., the molecular histology. The peptide/protein MALDI-IMS studies of neural structures such as OB are hampered by its very soft consistency and large amounts of lipids in these tissues. In this chapter, we describe how to analyze OB protein/peptide signals employing the MALDI-IMS. To circumvent the limitations inherent to the analysis of the neural tissues, we used a specific workflow including a nonstandard OCT-free cryo-slicing protocol followed by Carnoy delipidization and an automated matrix spray. Our goal is to provide the reader with guidelines for the study of the neural tissues using MALDI-IMS, highlighting the advantages and limitations of this approach.

Key words

Olfactory bulb MALDI-IMS Imaging mass spectrometry Molecular histology 

References

  1. 1.
    Longuespee R, Casadonte R, Kriegsmann M, Pottier C, Picard de Muller G, Delvenne P, Kriegsmann J, De Pauw E (2016) MALDI mass spectrometry imaging: a cutting-edge tool for fundamental and clinical histopathology. Proteomics Clin Appl 10(7):701–719. doi:10.1002/prca.201500140 CrossRefPubMedGoogle Scholar
  2. 2.
    Cole LM, Clench MR (2015) Mass spectrometry imaging for the proteomic study of clinical tissue. Proteomics Clin Appl 9(3–4):335–341. doi:10.1002/prca.201400103 CrossRefPubMedGoogle Scholar
  3. 3.
    Rodrigo MA, Zitka O, Krizkova S, Moulick A, Adam V, Kizek R (2014) MALDI-TOF MS as evolving cancer diagnostic tool: a review. J Pharm Biomed Anal 95:245–255. doi:10.1016/j.jpba.2014.03.007. S0731-7085(14)00132-0 [pii]CrossRefPubMedGoogle Scholar
  4. 4.
    Zaima N, Goto-Inoue N, Moriyama T (2014) Matrix-assisted laser desorption/ionization imaging mass spectrometry: new technology for vascular pathology. J Vasc Res 51(2):144–148. doi:10.1159/000362123. 000362123 [pii]CrossRefPubMedGoogle Scholar
  5. 5.
    Vegvari A (2015) Drug localizations in tissue by mass spectrometry imaging. Biomark Med 9(9):869–876. doi:10.2217/bmm.15.64 CrossRefPubMedGoogle Scholar
  6. 6.
    Chaurand P, Norris JL, Cornett DS, Mobley JA, Caprioli RM (2006) New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. J Proteome Res 5(11):2889–2900. doi:10.1021/pr060346u CrossRefPubMedGoogle Scholar
  7. 7.
    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(4):493–496. doi:10.1038/86573. 86573 [pii]CrossRefPubMedGoogle Scholar
  8. 8.
    Stoeckli M, Farmer TB, Caprioli RM (1999) Automated mass spectrometry imaging with a matrix-assisted laser desorption ionization time-of-flight instrument. J Am Soc Mass Spectrom 10(1):67–71. doi:10.1016/S1044-0305(98)00126-3. S1044-0305(98)00126-3 [pii]CrossRefPubMedGoogle Scholar
  9. 9.
    Fournier I, Wisztorski M, Salzet M (2008) Tissue imaging using MALDI-MS: a new frontier of histopathology proteomics. Expert Rev Proteomics 5(3):413–424. doi:10.1586/14789450.5.3.413 CrossRefPubMedGoogle Scholar
  10. 10.
    Hardesty WM, Caprioli RM (2008) In situ molecular imaging of proteins in tissues using mass spectrometry. Anal Bioanal Chem 391(3):899–903. doi:10.1007/s00216-008-1972-5 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Beine B, Diehl HC, Meyer HE, Henkel C (2016) Tissue MALDI mass spectrometry imaging (MALDI MSI) of peptides. Methods Mol Biol 1394:129–150. doi:10.1007/978-1-4939-3341-9_10 CrossRefPubMedGoogle Scholar
  12. 12.
    Yalcin EB, de la Monte SM (2015) Review of matrix-assisted laser desorption ionization-imaging mass spectrometry for lipid biochemical histopathology. J Histochem Cytochem 63(10):762–771. doi:10.1369/0022155415596202. 0022155415596202 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Miura D, Fujimura Y, Wariishi H (2012) In situ metabolomic mass spectrometry imaging: recent advances and difficulties. J Proteome 75(16):5052–5060. doi:10.1016/j.jprot.2012.02.011. S1874-3919(12)00092-9 [pii]CrossRefGoogle Scholar
  14. 14.
    Hillenkamp F, Karas M (1990) Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol 193:280–295. 0076-6879(90)93420-P [pii]CrossRefPubMedGoogle Scholar
  15. 15.
    Chaurand P, Schwartz SA, Billheimer D, BJ X, Crecelius A, Caprioli RM (2004) Integrating histology and imaging mass spectrometry. Anal Chem 76(4):1145–1155. doi:10.1021/ac0351264 CrossRefPubMedGoogle Scholar
  16. 16.
    Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69(23):4751–4760CrossRefPubMedGoogle Scholar
  17. 17.
    Ogrinc Potocnik N, Porta T, Becker M, Heeren RM, Ellis SR (2015) Use of advantageous, volatile matrices enabled by next-generation high-speed matrix-assisted laser desorption/ionization time-of-flight imaging employing a scanning laser beam. Rapid Commun Mass Spectrom 29(23):2195–2203. doi:10.1002/rcm.7379 CrossRefPubMedGoogle Scholar
  18. 18.
    Iloro I, Bueno A, Calvo J, Urreta H, Elortza F (2016) Langartech: a custom-made MALDI matrix sprayer for MALDI imaging mass spectrometry. J Lab Autom 21(2):260–267. doi:10.1177/2211068215607320. 2211068215607320 [pii]CrossRefPubMedGoogle Scholar
  19. 19.
    Lou S, Balluff B, Cleven AH, Bovee JV, McDonnell LA (2016) An experimental guideline for the analysis of histologically heterogeneous tumors by MALDI-TOF mass spectrometry imaging. Biochim Biophys Acta. doi:10.1016/j.bbapap.2016.09.020. S1570-9639(16)30205-9 [pii]Google Scholar
  20. 20.
    Mourino-Alvarez L, Iloro I, de la Cuesta F, Azkargorta M, Sastre-Oliva T, Escobes I, Lopez-Almodovar LF, Sanchez PL, Urreta H, Fernandez-Aviles F, Pinto A, Padial LR, Akerstrom F, Elortza F, Barderas MG (2016) MALDI-imaging mass spectrometry: a step forward in the anatomopathological characterization of stenotic aortic valve tissue. Sci Rep 6:27106. doi:10.1038/srep27106. srep27106 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Reyzer ML, Caldwell RL, Dugger TC, Forbes JT, Ritter CA, Guix M, Arteaga CL, Caprioli RM (2004) Early changes in protein expression detected by mass spectrometry predict tumor response to molecular therapeutics. Cancer Res 64(24):9093–9100. doi:10.1158/0008-5472.CAN-04-2231. 64/24/9093 [pii]CrossRefPubMedGoogle Scholar
  22. 22.
    Atkinson SJ, Loadman PM, Sutton C, Patterson LH, Clench MR (2007) Examination of the distribution of the bioreductive drug AQ4N and its active metabolite AQ4 in solid tumours by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom 21(7):1271–1276. doi:10.1002/rcm.2952 CrossRefPubMedGoogle Scholar
  23. 23.
    Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM (2006) Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. Anal Chem 78(18):6448–6456. doi:10.1021/ac060788p CrossRefPubMedGoogle Scholar
  24. 24.
    Norris JL, Caprioli RM (2013) Imaging mass spectrometry: a new tool for pathology in a molecular age. Proteomics Clin Appl 7(11–12):733–738. doi:10.1002/prca.201300055 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Schwamborn K, Caprioli RM (2010) Molecular imaging by mass spectrometry—looking beyond classical histology. Nat Rev Cancer 10(9):639–646. doi:10.1038/nrc2917. nrc2917 [pii]CrossRefPubMedGoogle Scholar
  26. 26.
    Aichler M, Walch A (2015) MALDI imaging mass spectrometry: current frontiers and perspectives in pathology research and practice. Lab Investig 95(4):422–431. doi:10.1038/labinvest.2014.156. labinvest2014156 [pii]CrossRefPubMedGoogle Scholar
  27. 27.
    Seeley EH, Caprioli RM (2012) 3D imaging by mass spectrometry: a new frontier. Anal Chem 84(5):2105–2110. doi:10.1021/ac2032707 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Deutskens F, Yang J, Caprioli RM (2011) High spatial resolution imaging mass spectrometry and classical histology on a single tissue section. J Mass Spectrom 46(6):568–571. doi:10.1002/jms.1926 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Sinha TK, Khatib-Shahidi S, Yankeelov TE, Mapara K, Ehtesham M, Cornett DS, Dawant BM, Caprioli RM, Gore JC (2008) Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging. Nat Methods 5(1):57–59. doi:10.1038/nmeth1147. nmeth1147 [pii]CrossRefPubMedGoogle Scholar
  30. 30.
    Schneider SA, Boettner M, Alexoudi A, Zorenkov D, Deuschl G, Wedel T (2016) Can we use peripheral tissue biopsies to diagnose Parkinson's disease? A review of the literature. Eur J Neurol 23(2):247–261. doi:10.1111/ene.12753 CrossRefPubMedGoogle Scholar
  31. 31.
    Christen-Zaech S, Kraftsik R, Pillevuit O, Kiraly M, Martins R, Khalili K, Miklossy J (2003) Early olfactory involvement in Alzheimer’s disease. Can J Neurol Sci 30(1):20–25CrossRefPubMedGoogle Scholar
  32. 32.
    Ferreyra-Moyano H, Barragan E (1989) The olfactory system and Alzheimer’s disease. Int J Neurosci 49(3–4):157–197CrossRefPubMedGoogle Scholar
  33. 33.
    Li J, Gu CZ, Su JB, Zhu LH, Zhou Y, Huang HY, Liu CF (2016) Changes in olfactory bulb volume in Parkinson’s disease: a systematic review and meta-analysis. PLoS One 11(2):e0149286. doi:10.1371/journal.pone.0149286. PONE-D-15-43501 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Meissner WG (2012) When does Parkinson’s disease begin? From prodromal disease to motor signs. Rev Neurol (Paris) 168(11):809–814. doi:10.1016/j.neurol.2012.07.004. S0035-3787(12)00883-1 [pii]CrossRefGoogle Scholar
  35. 35.
    McDonnell LA, Heeren RM (2007) Imaging mass spectrometry. Mass Spectrom Rev 26(4):606–643. doi:10.1002/mas.20124 CrossRefPubMedGoogle Scholar
  36. 36.
    Agar NY, Kowalski JM, Kowalski PJ, Wong JH, Agar JN (2010) Tissue preparation for the in situ MALDI MS imaging of proteins, lipids, and small molecules at cellular resolution. Methods Mol Biol 656:415–431. doi:10.1007/978-1-60761-746-4_24 CrossRefPubMedGoogle Scholar
  37. 37.
    Agar NY, Yang HW, Carroll RS, Black PM, Agar JN (2007) Matrix solution fixation: histology-compatible tissue preparation for MALDI mass spectrometry imaging. Anal Chem 79(19):7416–7423. doi:10.1021/ac071460e CrossRefPubMedGoogle Scholar
  38. 38.
    Bank HL, Brockbank KG (1987) Basic principles of cryobiology. J Card Surg 2(1 Suppl):137–143CrossRefPubMedGoogle Scholar
  39. 39.
    Mainini V, Lalowski M, Gotsopoulos A, Bitsika V, Baumann M, Magni F (2015) MALDI-imaging mass spectrometry on tissues. Methods Mol Biol 1243:139–164. doi:10.1007/978-1-4939-1872-0_8 CrossRefPubMedGoogle Scholar
  40. 40.
    Oetjen J, Lachmund D, Palmer A, Alexandrov T, Becker M, Boskamp T, Maass P (2016) An approach to optimize sample preparation for MALDI imaging MS of FFPE sections using fractional factorial design of experiments. Anal Bioanal Chem 408(24):6729–6740. doi:10.1007/s00216-016-9793-4 CrossRefPubMedGoogle Scholar
  41. 41.
    Aoki Y, Toyama A, Shimada T, Sugita T, Aoki C, Umino Y, Suzuki A, Aoki D, Daigo Y, Nakamura Y, Sato TA (2007) A novel method for analyzing formalin-fixed paraffin embedded (FFPE) tissue sections by mass spectrometry imaging. Proc Jpn Acad Ser B Phys Biol Sci 83(7):205–214. doi:10.2183/pjab/83.205. 83_205 [pii]CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kitamoto Y, Maeda H (1980) Reevaluation of the reaction of formaldehyde at low concentration with amino acids. J Biochem 87(5):1519–1530CrossRefPubMedGoogle Scholar
  43. 43.
    Altelaar AF, van Minnen J, Jimenez CR, Heeren RM, Piersma SR (2005) Direct molecular imaging of Lymnaea stagnalis nervous tissue at subcellular spatial resolution by mass spectrometry. Anal Chem 77(3):735–741. doi:10.1021/ac048329g CrossRefPubMedGoogle Scholar
  44. 44.
    Kruse R, Sweedler JV (2003) Spatial profiling invertebrate ganglia using MALDI MS. J Am Soc Mass Spectrom 14(7):752–759. doi:10.1016/S1044-0305(03)00288-5. S1044030503002885 [pii]CrossRefPubMedGoogle Scholar
  45. 45.
    Martin-Lorenzo M, Balluff B, Maroto AS, Carreira RJ, van Zeijl RJ, Gonzalez-Calero L, de la Cuesta F, Barderas MG, Lopez-Almodovar LF, Padial LR, McDonnell LA, Vivanco F, Alvarez-Llamas G (2015) Molecular anatomy of ascending aorta in atherosclerosis by MS imaging: specific lipid and protein patterns reflect pathology. J Proteome 126:245–251. doi:10.1016/j.jprot.2015.06.005. S1874-3919(15)30042-7 [pii]CrossRefGoogle Scholar
  46. 46.
    Caldwell RL, Caprioli RM (2005) Tissue profiling by mass spectrometry: a review of methodology and applications. Mol Cell Proteomics 4(4):394–401. doi:10.1074/mcp.R500006-MCP200. R500006-MCP200 [pii]CrossRefPubMedGoogle Scholar
  47. 47.
    Schwartz SA, Reyzer ML, Caprioli RM (2003) Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. J Mass Spectrom 38(7):699–708. doi:10.1002/jms.505 CrossRefPubMedGoogle Scholar
  48. 48.
    Van de Plas R, Ojeda F, Dewil M, Van Den Bosch L, De Moor B, Waelkens E (2007) Prospective exploration of biochemical tissue composition via imaging mass spectrometry guided by principal component analysis. Pac Symp Biocomput:458–469Google Scholar
  49. 49.
    McCombie G, Staab D, Stoeckli M, Knochenmuss R (2005) Spatial and spectral correlations in MALDI mass spectrometry images by clustering and multivariate analysis. Anal Chem 77(19):6118–6124. doi:10.1021/ac051081q CrossRefPubMedGoogle Scholar
  50. 50.
    Holland JH (1992) Adaptation in natural and artificial systems: an introductory analysis with applications to biology, control and artificial intelligence. MIT Press, CambridgeGoogle Scholar
  51. 51.
    Hammer B, Strickert M, Villmann T (2005) Supervised neural gas with general similarity measure. Neural Process Lett 21(1):21–44. doi:10.1007/s11063-004-3255-2 CrossRefGoogle Scholar
  52. 52.
    Vapnik VN (1995) The nature of statistical learning theory. Springer-Verlag, New YorkCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Ibon Iloro
    • 1
  • Joaquín Fernández-Irigoyen
    • 2
  • Iraide Escobes
    • 1
  • Mikel Azkargorta
    • 1
  • Enrique Santamaría
    • 2
  • Felix Elortza
    • 1
  1. 1.Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIIIDerioSpain
  2. 2.Clinical Neuroproteomics Unit, Navarrabiomed, Navarra HealthDepartmentPublic University of Navarra,Proteored-Institute of Health Carlos III (ISCIII), Navarra Institute for Health Research (IdiSNA)PamplonaSpain

Personalised recommendations