Measurement of F4-Neuroprostanes by Gas Chromatography-Mass Spectrometry/Negative Ion Chemical Ionization

  • Nathalie Bernoud-Hubac
  • L. Jackson RobertsII
Part of the Methods in Pharmacology and Toxicology book series (MIPT)


Oxidative damage has been strongly implicated in the pathogenesis of a number of neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD) (1, 2, 3, 4, 5, 6, 7, 8, 9). Several years ago, we reported the discovery of the formation of F2-isoprostanes (F2-IsoPs), which are prostaglandin F2-like compounds formed in vivo nonenzymatically as products of free radical-induced oxidation of arachidonic acid (10). More recently we described the formation of IsoP-like compounds in vivo from free radical-induced oxidation of docosahexaenoic acid (DHA) (5). DHA is a fatty acid that is uniquely enriched in the brain, particularly the gray matter, where it comprises approx 25–35% of the total fatty acids in aminophospholipids (11,12). Our motive for exploring whether IsoP-like compounds are formed from oxidation of DHA derives from our hypothesis that measurement of such compounds may provide a unique and sensitive biomarker of oxidative neuronal injury in the brain. Accordingly, we have termed these compounds neuroprostanes (NPs).


Amyotrophic Lateral Sclerosis Peroxyl Radical Trimethylsilyl Ether Plastic Test Tube Pentafluorobenzyl Bromide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Markesbery, W. R. (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic. Biol. Med. 23, 134–147.PubMedCrossRefGoogle Scholar
  2. 2.
    Markesbery, W. R. (1999) The role of oxidative stress in Alzheimer disease. Arch. Neurol. 56, 1449–1452.PubMedCrossRefGoogle Scholar
  3. 3.
    Simonian, N. A. and Coyle, J. T. (1996) Oxidative stress in neurodegenerative diseases. Annu. Rev. Pharmacol. Toxicol. 36, 83–106.PubMedCrossRefGoogle Scholar
  4. 4.
    Perry, G., Nunomura, A., Hirai, K., Takeda, A., Aliev, G., and Smith, M. A. (2000) Oxidative damage in Alzheimer’s disease: the metabolic dimension. Int. J. Dev. Neurosci. 18,417–421.PubMedCrossRefGoogle Scholar
  5. 5.
    Roberts, L. J., 2nd, Montine, T. J., Markesbery, W. R., Tapper, A. R., Hardy, P., Chemtob, S., et al. (1998) Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J. Biol. Chem. 273, 13,605–13,612.PubMedCrossRefGoogle Scholar
  6. 6.
    Montine, T. J., Markesbery, W. R., Morrow, J. D., and Roberts, L. J. (1998) Cerebrospinal fluid F2-isoprostane levels are increased in Alzheimer’s disease. Ann. Neurol. 44, 410–413.PubMedCrossRefGoogle Scholar
  7. 7.
    Montine, T. J., Beal, M. F., Cudkowicz, M. E., O’Donnell, H., Margolin, R. A., McFarland, L., et al. (1999) Increased CSF F2-isoprostane concentration in probable AD. Neurology 52, 562–565.PubMedGoogle Scholar
  8. 8.
    Montine, T. J., Beal, M. F., Robertson, D., Cudkowicz, M. E., Biaggioni, I., O’Donnell, H., et al. (1999) Cerebrospinal fluid F2-isoprostanes are elevated in Huntington’s disease. Neurology 52, 1104–1105.PubMedGoogle Scholar
  9. 9.
    Reich, E. E., Markesbery, W. R., Roberts, L. J., Swift, L. L., Morrow, J. D., and Montine, T. J. (2001) Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer’s disease. Am. J. Pathol. 158, 293–297.PubMedCrossRefGoogle Scholar
  10. 10.
    Morrow, J. D., Hill, K. E., Burk, R. F., Nammour, T. M., Badr, K. F., and Roberts, L. J., 2nd (1990) A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc. Natl. Acad. Sci. USA 87, 9383–9387.PubMedCrossRefGoogle Scholar
  11. 11.
    Salem, N., Jr., Kim, H.-Y., and Yergery, J.A. (1986) Docosahexaenoic acid: membrane function and metaolism, in Health Effects of Polyunsaturated Fatty Acids in Seafoods (Simopoulos, A. P., Kifer, R. R., and Martin, R. E., eds.), Academic Press, Orlando, FL, pp. 263–317.Google Scholar
  12. 12.
    Skinner, E. R., Watt, C., Besson, J. A., and Best, P. V. (1993) Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer’s disease and control subjects. Brain 116, 717–725.PubMedCrossRefGoogle Scholar
  13. 13.
    Taber, D. F., Morrow, J. D., Roberts, L. J., 2nd (1997) A nomenclature system for the isoprostanes. Prostaglandins 53, 63–67.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc.,Totowa, NJ 2003

Authors and Affiliations

  • Nathalie Bernoud-Hubac
    • 1
  • L. Jackson RobertsII
    • 1
  1. 1.Departments of Pharmacology and MedicineVanderbilt UniversityNashville

Personalised recommendations