1932

Abstract

Neuropeptides are important mediators in the functionality of the brain and other neurological organs. Because neuropeptides exist in a wide range of concentrations, appropriate characterization methods are needed to provide dynamic, chemical, and spatial information. Mass spectrometry and compatible tools have been a popular choice in analyzing neuropeptides. There have been several advances and challenges, both of which are the focus of this review. Discussions range from sample collection to bioinformatic tools, although avenues such as quantitation and imaging are included. Further development of the presented methods for neuropeptidomic mass spectrometric analysis is inevitable, which will lead to a further understanding of the complex interplay of neuropeptides and other signaling molecules in the nervous system.

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2015-07-22
2024-04-24
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Literature Cited

  1. Li LJ, Sweedler JV. 1.  2008. Peptides in the brain: mass spectrometry-based measurement approaches and challenges. Annu. Rev. Anal. Chem. 1:451–83 [Google Scholar]
  2. Hökfelt T, Broberger C, Xu Z-QD, Sergeyev V, Ubink R, Diez M. 2.  2000. Neuropeptides: an overview. Neuropharmacology 39:1337–56 [Google Scholar]
  3. Frese CK, Boender AJ, Mohammed S, Heck AJ, Adan RA, Altelaar AF. 3.  2013. Profiling of diet-induced neuropeptide changes in rat brain by quantitative mass spectrometry. Anal. Chem. 85:4594–604 [Google Scholar]
  4. Morimoto R, Satoh F, Murakami O, Totsune K, Saruta M. 4.  et al. 2008. Expression of peptide YY in human brain and pituitary tissues. Nutrition 24:878–84 [Google Scholar]
  5. Van Eeckhaut A, Maes K, Aourz N, Smolders I, Michotte Y. 5.  2011. The absolute quantification of endogenous levels of brain neuropeptides in vivo using LC-MS/MS. Bioanalysis 3:1271–85 [Google Scholar]
  6. von Bohlen und Halbach O. 6.  2005. The renin-angiotensin system in the mammalian central nervous system. Curr. Protein Pept. Sci. 6:355–71 [Google Scholar]
  7. Yu Q, OuYang C, Liang Z, Li L. 7.  2014. Mass spectrometric characterization of the crustacean neuropeptidome. EuPA Open Proteomics 3:152–70 [Google Scholar]
  8. Schmerberg CM, Li LJ. 8.  2013. Mass spectrometric detection of neuropeptides using affinity-enhanced microdialysis with antibody-coated magnetic nanoparticles. Anal. Chem. 85:915–22 [Google Scholar]
  9. Yew JY. 9.  et al. 2005. Mass spectrometric map of neuropeptide expression in Ascaris suum. J. Comp. Neurol. 488:396–413 [Google Scholar]
  10. Bruzzone F, Lectez B, Tollemer H, Leprince J, Dujardin C. 10.  et al. 2006. Anatomical distribution and biochemical characterization of the novel RFamide peptide 26RFa in the human hypothalamus and spinal cord. J. Neurochem. 99:616–27 [Google Scholar]
  11. Jarecki JL, Viola IR, Andersen KM, Miller AH, Ramaker MA. 11.  et al. 2013. Three independent techniques localize expression of transcript afp-11 and its bioactive peptide products to the paired AVK neurons in Ascaris suum: in situ hybridization, immunocytochemistry, and single cell mass spectrometry. ACS Chem. Neurosci. 4:418–34 [Google Scholar]
  12. Hui LM, Xiang F, Zhang YZ, Li LJ. 12.  2012. Mass spectrometric elucidation of the neuropeptidome of a crustacean neuroendocrine organ. Peptides 36:230–39 [Google Scholar]
  13. Dowell JA, Vander Heyden W, Li L. 13.  2006. Rat neuropeptidomics by LC-MS/MS and MALDI-FTMS: enhanced dissection and extraction techniques coupled with 2D RP-RP HPLC. J. Proteome Res. 5:3368–75 [Google Scholar]
  14. Hui LM. 14.  et al. 2013. Mass spectrometric characterization of the neuropeptidome of the ghost crab Ocypode ceratophthalma (Brachyura, Ocypodidae). Gen. Comp. Endocrinol. 184:22–34 [Google Scholar]
  15. Castro LM, Cavalcanti DMLP, Rioli V, Icimoto MY, Gozzo FC. 15.  et al. 2014. Peptidomic analysis of the neurolysin-knockout mouse brain. J. Proteomics 111:238–48 [Google Scholar]
  16. Predel R, Neupert S, Garczynski SF, Crim JW, Brown MR. 16.  et al. 2010. Neuropeptidomics of the mosquito Aedes aegypti. J. Proteome Res. 9:2006–15 [Google Scholar]
  17. Xie F, Romanova EV, Sweedler JV. 17.  2011. Neuropeptidomics of the mammalian brain. Neuroproteomics KW Li 57229–42 New York: Humana [Google Scholar]
  18. Southey BR, Lee JE, Zamdborg L, Atkins N Jr, Mitchell JW. 18.  et al. 2014. Comparing label-free quantitative peptidomics approaches to characterize diurnal variation of peptides in the rat suprachiasmatic nucleus. Anal. Chem. 86:443–52 [Google Scholar]
  19. Che FY, Lim J, Pan H, Biswas R, Fricker LD. 19.  2005. Quantitative neuropeptidomics of microwave-irradiated mouse brain and pituitary. Mol. Cell. Proteomics 4:1391–405 [Google Scholar]
  20. Parkin MC, Wei H, O'Callaghan JP, Kennedy RT. 20.  2005. Sample-dependent effects on the neuropeptidome detected in rat brain tissue preparations by capillary liquid chromatography with tandem mass spectrometry. Anal. Chem. 77:6331–38 [Google Scholar]
  21. Colgrave ML, Xi L, Lehnert SA, Flatscher-Bader T, Wadenstein H. 21.  et al. 2011. Neuropeptide profiling of the bovine hypothalamus: thermal stabilization is an effective tool in inhibiting post-mortem degradation. Proteomics 11:1264–76 [Google Scholar]
  22. Stingl C, Soderquist M, Karlsson O, Boren M, Luider TM. 22.  2014. Uncovering effects of ex vivo protease activity during proteomics and peptidomics sample extraction in rat brain tissue by oxygen-18 labeling. J. Proteome Res. 13:2807–17 [Google Scholar]
  23. Sturm RM, Greer T, Woodards N, Gemperline E, Li LJ. 23.  2013. Mass spectrometric evaluation of neuropeptidomic profiles upon heat stabilization treatment of neuroendocrine tissues in crustaceans. J. Proteome Res. 12:743–52 [Google Scholar]
  24. Zhang XZ, Petruzziello F, Zani F, Fouillen L, Andren PE. 24.  et al. 2012. High identification rates of endogenous neuropeptides from mouse brain. J. Proteome Res. 11:2819–27 [Google Scholar]
  25. Bai L, Romanova EV, Sweedler JV. 25.  2011. Distinguishing endogenous D-amino acid-containing neuropeptides in individual neurons using tandem mass spectrometry. Anal. Chem. 83:2794–800 [Google Scholar]
  26. Neupert S, Predel R. 26.  2010. Peptidomic analysis of single identified neurons. See Ref. 148 137–44
  27. Neupert S, Rubakhin SS, Sweedler JV. 27.  2012. Targeted single-cell microchemical analysis: MS-based peptidomics of individual paraformaldehyde-fixed and immunolabeled neurons. Chem. Biol. 19:1010–19 [Google Scholar]
  28. Neupert S, Fusca D, Schachtner J, Kloppenburg P, Predel R. 28.  2012. Toward a single-cell-based analysis of neuropeptide expression in Periplaneta americana antennal lobe neurons. J. Comp. Neurol. 520:694–716 [Google Scholar]
  29. Rubakhin SS, Sweedler JV. 29.  2008. Quantitative measurements of cell-cell signaling peptides with single-cell MALDI MS. Anal. Chem. 80:7128–36 [Google Scholar]
  30. Romanova EV, Aerts JT, Croushore CA, Sweedler JV. 30.  2014. Small-volume analysis of cell-cell signaling molecules in the brain. Neuropsychopharmacology 39:50–64 [Google Scholar]
  31. Torregrossa MM, Kalivas PW. 31.  2008. Microdialysis and the neurochemistry of addiction. Pharmacol. Biochem. Behav. 90:261–72 [Google Scholar]
  32. Mabrouk OS, Kennedy RT. 32.  2012. Simultaneous oxytocin and arg-vasopressin measurements in microdialysates using capillary liquid chromatography–mass spectrometry. J. Neurosci. Methods 209:127–33 [Google Scholar]
  33. Li Q, Zubieta JK, Kennedy RT. 33.  2009. Practical aspects of in vivo detection of neuropeptides by microdialysis coupled off-line to capillary LC with multistage MS. Anal. Chem. 81:2242–50 [Google Scholar]
  34. Behrens HL, Li LJ. 34.  2010. Monitoring neuropeptides in vivo via microdialysis and mass spectrometry. See Ref. 148 57–73
  35. Zhou Y, Mabrouk OS, Kennedy RT. 35.  2013. Rapid preconcentration for liquid chromatography-mass spectrometry assay of trace level neuropeptides. J. Am. Soc. Mass Spectrom. 24:1700–9 [Google Scholar]
  36. Inutan ED, Wang BX, Trimpin S. 36.  2011. Commercial intermediate pressure MALDI ion mobility spectrometry mass spectrometer capable of producing highly charged laserspray ionization ions. Anal. Chem. 83:678–84 [Google Scholar]
  37. McEwen CN, Larsen BS, Trimpin S. 37.  2010. Laserspray ionization on a commercial atmospheric pressure-MALDI mass spectrometer ion source: selecting singly or multiply charged ions. Anal. Chem. 82:4998–5001 [Google Scholar]
  38. Trimpin S, Inutan ED, Herath TN, McEwen CN. 38.  2010. Laserspray ionization, a new atmospheric pressure MALDI method for producing highly charged gas-phase ions of peptides and proteins directly from solid solutions. Mol. Cell. Proteomics 9:362–67 [Google Scholar]
  39. Li J, Inutan ED, Wang B, Lietz CB, Green DR. 39.  et al. 2012. Matrix assisted ionization: new aromatic and nonaromatic matrix compounds producing multiply charged lipid, peptide, and protein ions in the positive and negative mode observed directly from surfaces. J. Am. Soc. Mass Spectrom. 23:1625–43 [Google Scholar]
  40. Trimpin S, Inutan ED. 40.  2013. Matrix assisted ionization in vacuum, a sensitive and widely applicable ionization method for mass spectrometry. J. Am. Soc. Mass Spectrom. 24:722–32 [Google Scholar]
  41. Trimpin S, Inutan ED, Herath TN, McEwen CN. 41.  2010. Matrix-assisted laser desorption/ionization mass spectrometry method for selectively producing either singly or multiply charged molecular ions. Anal. Chem. 82:11–15 [Google Scholar]
  42. Ma MM, Sturm RM, Kutz-Naber KK, Fu Q, Li LJ. 42.  2009. Immunoaffinity-based mass spectrometric characterization of the FMRFamide-related peptide family in the pericardial organ of Cancer borealis. Biochem. Biophys. Res. Commun. 390:325–30 [Google Scholar]
  43. Dowell JA, Frost DC, Zhang J, Li LJ. 43.  2008. Comparison of two-dimensional fractionation techniques for shotgun proteomics. Anal. Chem. 80:6715–23 [Google Scholar]
  44. Zhang GD, Zhang YZ, Fast DM, Lin ZS, Steenwyk R. 44.  2011. Ultra sensitive quantitation of endogenous oxytocin in rat and human plasma using a two-dimensional liquid chromatography–tandem mass spectrometry assay. Anal. Biochem. 416:45–52 [Google Scholar]
  45. Zhang ZC, Ye H, Wang JH, Hui LM, Li LJ. 45.  2012. Pressure-assisted capillary electrophoresis coupling with matrix-assisted laser desorption/ionization-mass spectrometric imaging for quantitative analysis of complex peptide mixtures. Anal. Chem. 84:7684–91 [Google Scholar]
  46. Wang JH, Ye H, Zhang Z, Xiang F, Girdaukas G, Li L. 46.  2011. Advancing matrix-assisted laser desorption/ionization-mass spectrometric imaging for capillary electrophoresis analysis of peptides. Anal. Chem. 83:3462–69 [Google Scholar]
  47. Zhong XF, Zhang ZC, Jiang S, Li LJ. 47.  2014. Recent advances in coupling capillary electrophoresis-based separation techniques to ESI and MALDI-MS. Electrophoresis 35:1214–25 [Google Scholar]
  48. Medina-Casanellas S, Domínguez-Vega E, Benavente F, Sanz-Nebt V, Somsen GW, de Jong GJ. 48.  2014. Low-picomolar analysis of peptides by on-line coupling of fritless solid-phase extraction to sheathless capillary electrophoresis-mass spectrometry. J. Chromatogr. A 13281–6
  49. Soper MT, DeToma AS, Hyung SJ, Lim MH, Ruotolo BT. 49.  2013. Amyloid-β-neuropeptide interactions assessed by ion mobility-mass spectrometry. Phys. Chem. Chem. Phys. 15:8952–61 [Google Scholar]
  50. Jia CX, Wu Z, Lietz CB, Liang Z, Cui Q, Li L. 50.  2014. Gas-phase ion isomer analysis reveals the mechanism of peptide sequence scrambling. Anal. Chem. 86:2917–24 [Google Scholar]
  51. Shvartsburg AA, Creese AJ, Smith RD, Cooper HJ. 51.  2010. Separation of peptide isomers with variant modified sites by high-resolution differential ion mobility spectrometry. Anal. Chem. 82:8327–34 [Google Scholar]
  52. Jia CX, Lietz CB, Yu Q, Li LJ. 52.  2014. Site-specific characterization of d-amino acid containing peptide epimers by ion mobility spectrometry. Anal. Chem. 86:2972–81 [Google Scholar]
  53. Kanu AB, Dwivedi P, Tam M, Matz L, Hill HH. 53.  2008. Ion mobility-mass spectrometry. J. Mass Spectrom. 43:1–22 [Google Scholar]
  54. Shvartsburg AA, Anderson GA, Smith RD. 54.  2013. Pushing the frontier of high-definition ion mobility spectrometry using FAIMS. Mass Spectrom. 2:Spec. IssueS0011 [Google Scholar]
  55. Hayakawa E, Menschaert G, De Bock PJ, Luyten W, Gevaert K. 55.  et al. 2013. Improving the identification rate of endogenous peptides using electron transfer dissociation and collision-induced dissociation. J. Proteome Res. 12:5410–21 [Google Scholar]
  56. Yew JY, Dikler S, Stretton AO. 56.  2003. De novo sequencing of novel neuropeptides directly from Ascaris suum tissue using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight. Rapid Commun. Mass Spectrom. 17:2693–98 [Google Scholar]
  57. Ma MM, Kutz-Naber KK, Li LJ. 57.  2007. Methyl esterification assisted MALDI FTMS characterization of the orcokinin neuropeptide family. Anal. Chem. 79:673–81 [Google Scholar]
  58. Fu Q, Li LJ. 58.  2005. De novo sequencing of neuropeptides using reductive isotopic methylation and investigation of ESI QTOF MS/MS fragmentation pattern of neuropeptides with N-terminal dimethylation. Anal. Chem. 77:7783–95 [Google Scholar]
  59. Jia CX, Lietz CB, Ye H, Hui L, Yu Q. 59.  et al. 2013. A multi-scale strategy for discovery of novel endogenous neuropeptides in the crustacean nervous system. J. Proteomics 91:1–12 [Google Scholar]
  60. Ofer D, Linial M. 60.  2014. NeuroPID: a predictor for identifying neuropeptide precursors from metazoan proteomes. Bioinformatics 30:931–40 [Google Scholar]
  61. Southey BR, Amare A, Zimmerman TA, Rodriguez-Zas SL, Sweedler JV. 61.  2006. NeuroPred: a tool to predict cleavage sites in neuropeptide precursors and provide the masses of the resulting peptides. Nucleic Acids Res. 34:W267–72 [Google Scholar]
  62. Fälth M, Sköld K, Norman M, Svensson M, Fenyö D, Andren PE. 62.  2006. SwePep, a database designed for endogenous peptides and mass spectrometry. Mol. Cell. Proteomics 5:998–1005 [Google Scholar]
  63. Kim Y, Bark S, Hook V, Bandeira N. 63.  2011. NeuroPedia: neuropeptide database and spectral library. Bioinformatics 27:2772–73 [Google Scholar]
  64. Ma B, Zhang K, Hendrie C, Liang C, Li M. 64.  et al. 2003. PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry. Rapid Commun. Mass Spectrom. 17:2337–42 [Google Scholar]
  65. Baggerman G, Liu F, Wets G, Schoofs L. 65.  2005. Bioinformatic analysis of peptide precursor proteins. Trends Comp. Endocrinol. Neurobiol. 1040:59–65 [Google Scholar]
  66. Clynen E, Liu F, Husson SJ, Landuyt B, Hayakawa E. 66.  et al. 2010. Bioinformatic approaches to the identification of novel neuropeptide precursors. See Ref. 148 357–74
  67. Southey BR, Rodriguez-Zas SL, Sweedler JV. 67.  2009. Characterization of the prohormone complement in cattle using genomic libraries and cleavage prediction approaches. BMC Genomics 10:11 [Google Scholar]
  68. Fälth M, Svensson M, Nilsson A, Sköld K, Fenyö D, Andren PE. 68.  2008. Validation of endogenous peptide identifications using a database of tandem mass spectra. J. Proteome Res. 7:3049–53 [Google Scholar]
  69. Desiderio DM, Yamada S, Tanzer FS, Horton J, Trimble J. 69.  1981. High-performance liquid chromatographic and field desorption mass spectrometric measurement of picomole amounts of endogenous neuropeptides in biologic tissue. J. Chromatogr. 217:437–52 [Google Scholar]
  70. Kosanam H, Ramagiri S, Dass C. 70.  2009. Quantification of endogenous α- and γ-endorphins in rat brain by liquid chromatography-tandem mass spectrometry. Anal. Biochem. 392:83–89 [Google Scholar]
  71. Desiderio DM, Kai M. 71.  1983. Preparation of stable isotope-incorporated peptide internal standards for field desorption mass spectrometry quantification of peptides in biologic tissue. Biomed. Mass Spectrom. 10:471–79 [Google Scholar]
  72. Kusmierz JJ, Sumrada R, Desiderio DM. 72.  1990. Fast atom bombardment mass spectrometric quantitative analysis of methionine-enkephalin in human pituitary tissues. Anal. Chem. 62:2395–400 [Google Scholar]
  73. Dass C, Kusmierz JJ, Desiderio DM. 73.  1991. Mass spectrometric quantification of endogenous beta-endorphin. Biol. Mass Spectrom. 20:130–38 [Google Scholar]
  74. Desiderio DM, Zhu X. 74.  1998. Quantitative analysis of methionine enkephalin and β-endorphin in the pituitary by liquid secondary ion mass spectrometry and tandem mass spectrometry. J. Chromatogr. A 794:85–96 [Google Scholar]
  75. Gerber SA, Rush J, Stemman O, Kirschner MW, Gygi SP. 75.  2003. Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc. Natl. Acad. Sci. USA 100:6940–45 [Google Scholar]
  76. Kheterpal I, Kastin AJ, Mollah S, Yu C, Hsuchou H, Pan W. 76.  2009. Mass spectrometric quantification of MIF-1 in mouse brain by multiple reaction monitoring. Peptides 30:1276–81 [Google Scholar]
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