Skip to main content
SpringerLink
Log in

Pathophysiology of Olfactory Disorders and Potential Treatment Strategies

  • Taste and Smell Disorders (E Holbrook, Section Editor)
  • Published:
Current Otorhinolaryngology Reports Aims and scope Submit manuscript

Abstract

Olfactory disorders have been regarded in the past with a sense of therapeutic nihilism. However, there have been remarkable advances in chemosensory research over the past several years. The clinical importance of olfactory disorders is well established, and entities such as presbyosmia have gained considerable broad attention. Powerful basic science experimental approaches have revealed aspects of olfactory neuron physiology, olfactory tissue maintenance, and regeneration that provide new potential therapeutic targets for certain forms of olfactory dysfunction. Although many recent advances remain in pre-clinical stages, there is considerable reason for optimism regarding future approaches for treatment of patients with olfactory loss.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Murphy C, Schubert CR, Cruickshanks KJ, Klein BE, Klein R, Nondahl DM. Prevalence of olfactory impairment in older adults. JAMA. 2002;288(18):2307–12.

    Article  PubMed  Google Scholar 

  2. Gopinath B, Sue CM, Kifley A, Mitchell P. The association between olfactory impairment and total mortality in older adults. J Gerontol A Biol Sci Med Sci. 2012;67(2):204–9.

    Article  PubMed  Google Scholar 

  3. •• Pinto JM, Wroblewski KE, Kern DW, Schumm LP, McClintock MK. Olfactory dysfunction predicts 5-year mortality in older adults. PloS One. 2014;9(10):e107541. Presbyosmia is a strong predictor of 5-year mortality. In a large database sample of older U.S. adults, olfactory loss was identified as a biomarker for mortality.

  4. Paik SI, Lehman MN, Seiden AM, Duncan HJ, Smith DV. Human olfactory biopsy. The influence of age and receptor distribution. Arch Otolaryngol Head Neck Surg. 1992;118(7):731–8.

    Article  CAS  PubMed  Google Scholar 

  5. Weiler E, Farbman AI. Proliferation in the rat olfactory epithelium: age-dependent changes. J Neurosci. 1997;17(10):3610–22.

    CAS  PubMed  Google Scholar 

  6. Loo AT, Youngentob SL, Kent PF, Schwob JE. The aging olfactory epithelium: neurogenesis, response to damage, and odorant-induced activity. Int J Dev Neurosci. 1996;14(7–8):881–900.

    Article  CAS  PubMed  Google Scholar 

  7. • Jia C, Hegg CC. Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation. Neurobiol Aging. 2015;36(2):1045–56. Neuropeptide Y, which is a known basal cell mitogen, is found to decrease with age in mouse olfactory epithelium. This decrease may play a role in presbyosmia development.

  8. DeConde AS, Mace JC, Alt JA, Schlosser RJ, Smith TL, Soler ZM. Comparative effectiveness of medical and surgical therapy on olfaction in chronic rhinosinusitis: a prospective, multi-institutional study. Int Forum Allergy Rhinol. 2014;4(9):725–33.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kuperan AB, Lieberman SM, Jourdy DN, Al-Bar MH, Goldstein BJ, Casiano RR. The effect of endoscopic olfactory cleft polyp removal on olfaction. AM J Rhinol Allergy. 2015;29(4):309–13.

    Article  PubMed  Google Scholar 

  10. Bushdid C, Magnasco MO, Vosshall LB, Keller A. Humans can discriminate more than 1 trillion olfactory stimuli. Science. 2014;343(6177):1370–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Holbrook EH, Wu E, Curry WT, Lin DT, Schwob JE. Immunohistochemical characterization of human olfactory tissue. Laryngoscope. 2011;121(8):1687–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Buck L, Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 1991;65(1):175–87.

    Article  CAS  PubMed  Google Scholar 

  13. Mombaerts P, Wang F, Dulac C, Chao SK, Nemes A, Mendelsohn M, et al. Visualizing an olfactory sensory map. Cell. 1996;87(4):675–86.

    Article  CAS  PubMed  Google Scholar 

  14. Kulaga HM, Leitch CC, Eichers ER, Badano JL, Lesemann A, Hoskins BE, et al. Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat Genet. 2004;36(9):994–8.

    Article  CAS  PubMed  Google Scholar 

  15. Tadenev AL, Kulaga HM, May-Simera HL, Kelley MW, Katsanis N, Reed RR. Loss of Bardet–Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization, and axon targeting. PNAS. 2011;108(25):10320–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Williams CL, McIntyre JC, Norris SR, Jenkins PM, Zhang L, Pei Q, et al. Direct evidence for BBSome-associated intraflagellar transport reveals distinct properties of native mammalian cilia. Nat Commun. 2014;5:5813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Carr VM, Farbman AI. The dynamics of cell death in the olfactory epithelium. Exp Neurol. 1993;124(2):308–14.

    Article  CAS  PubMed  Google Scholar 

  18. Huard JM, Youngentob SL, Goldstein BJ, Luskin MB, Schwob JE. Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells. J Comp Neurol. 1998;400(4):469–86.

    Article  CAS  PubMed  Google Scholar 

  19. Goldstein BJ, Schwob JE. Analysis of the globose basal cell compartment in rat olfactory epithelium using GBC-1, a new monoclonal antibody against globose basal cells. J Neurosci. 1996;16(12):4005–16.

    CAS  PubMed  Google Scholar 

  20. Leung CT, Coulombe PA, Reed RR. Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci. 2007;10(6):720–6.

    Article  CAS  PubMed  Google Scholar 

  21. Chen M, Tian S, Yang X, Lane AP, Reed RR, Liu H. Wnt-responsive Lgr5(+) globose basal cells function as multipotent olfactory epithelium progenitor cells. J Neurosci. 2014;34(24):8268–76.

    Article  PubMed  PubMed Central  Google Scholar 

  22. • Goldstein BJ, Goss GM, Hatzistergos KE, Rangel EB, Seidler B, Saur D et al. Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. J Comp Neurol. 2015;523(1):15–31. The cell surface protein c-Kit is expressed by basal stem cells needed to produce new olfactory neurons in adult olfactory epithelium.

  23. Wang YZ, Yamagami T, Gan Q, Wang Y, Zhao T, Hamad S, et al. Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration. J Cell Sci. 2011;124(Pt 9):1553–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lane AP, Turner J, May L, Reed R. A genetic model of chronic rhinosinusitis-associated olfactory inflammation reveals reversible functional impairment and dramatic neuroepithelial reorganization. J Neurosci. 2010;30(6):2324–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. •• McIntyre JC, Davis EE, Joiner A, Williams CL, Tsai IC, Jenkins PM et al. Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model. Nat Med. 2012;18(9):1423–8. A mouse model of cilia disorder is proven to be anosmic. The anosmia is rescued by using viral-based gene therapy, providing proof-of-concept that some forms of sensorineural anosmia can be treated with viral gene therapy.

  26. Turner JH, May L, Reed RR, Lane AP. Reversible loss of neuronal marker protein expression in a transgenic mouse model for sinusitis-associated olfactory dysfunction. Am J Rhinol Allergy. 2010;24(3):192–6.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Graziadei GA, Graziadei PP. Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy. J Neurocytol. 1979;8(2):197–213.

    Article  CAS  PubMed  Google Scholar 

  28. Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L. Smell identification ability: changes with age. Science. 1984;226(4681):1441–3.

    Article  CAS  PubMed  Google Scholar 

  29. Holbrook EH, Leopold DA, Schwob JE. Abnormalities of axon growth in human olfactory mucosa. Laryngoscope. 2005;115(12):2144–54. doi:10.1097/01.MLG.0000181493.83661.CE.

    Article  PubMed  Google Scholar 

  30. Hansel DE, Eipper BA, Ronnett GV. Neuropeptide Y functions as a neuroproliferative factor. Nature. 2001;410(6831):940–4.

    Article  CAS  PubMed  Google Scholar 

  31. Goss GM, Chaudhari N, Hare JM, Nwojo R, Seidler B, Saur D, et al. Differentiation potential of individual olfactory c-Kit+ progenitors determined via multicolor lineage tracing. Dev Neurobiol. 2015;. doi:10.1002/dneu.22310.

    PubMed  Google Scholar 

  32. Bianco P, Cao X, Frenette PS, Mao JJ, Robey PG, Simmons PJ, et al. The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med. 2013;19(1):35–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Goldstein BJ, Fang H, Youngentob SL, Schwob JE. Transplantation of multipotent progenitors from the adult olfactory epithelium. Neuroreport. 1998;9(7):1611–7.

    Article  CAS  PubMed  Google Scholar 

  34. Jang W, Lambropoulos J, Woo JK, Peluso CE, Schwob JE. Maintaining epitheliopoietic potency when culturing olfactory progenitors. Exp Neurol. 2008;214(1):25–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Murrell W, Wetzig A, Donnellan M, Feron F, Burne T, Meedeniya A, et al. Olfactory mucosa is a potential source for autologous stem cell therapy for Parkinson’s disease. Stem Cells. 2008;26(8):2183–92.

    Article  CAS  PubMed  Google Scholar 

  36. Damm M, Pikart LK, Reimann H, Burkert S, Goktas O, Haxel B, et al. Olfactory training is helpful in postinfectious olfactory loss: a randomized, controlled, multicenter study. Laryngoscope. 2014;124(4):826–31.

    Article  PubMed  Google Scholar 

  37. Konstantinidis I, Tsakiropoulou E, Bekiaridou P, Kazantzidou C, Constantinidis J. Use of olfactory training in post-traumatic and postinfectious olfactory dysfunction. Laryngoscope. 2013;123(12):E85–90.

    Article  PubMed  Google Scholar 

  38. Altundag A, Cayonu M, Kayabasoglu G, Salihoglu M, Tekeli H, Saglam O, et al. Modified olfactory training in patients with postinfectious olfactory loss. Laryngoscope. 2015;125(8):1763–6.

    Article  PubMed  Google Scholar 

  39. Siopi E, Calabria S, Plotkine M, Marchand-Leroux C, Jafarian-Tehrani M. Minocycline restores olfactory bulb volume and olfactory behavior after traumatic brain injury in mice. J Neurotrauma. 2012;29(2):354–61.

    Article  PubMed  Google Scholar 

  40. Reden J, Herting B, Lill K, Kern R, Hummel T. Treatment of postinfectious olfactory disorders with minocycline: a double-blind, placebo-controlled study. Laryngoscope. 2011;121(3):679–82.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, 1120 NW 14th St, 5th Floor, Miami, FL, 33136, USA

    Stefania Goncalves & Bradley J. Goldstein

Authors
  1. Stefania Goncalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bradley J. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bradley J. Goldstein.

Ethics declarations

Conflict of Interest

Dr. Stefania Goncalves declares that she has no conflicts of interest. Dr. Bradley J. Goldstein reports grants from NIH (DC013556), during the conduct of the study.

Human and Animal Rights and Informed Consent

The Institutional Animal Care and Use Committee of the University of Miami approved all experiments.

Additional information

This article is part of the Topical Collection on Taste and Smell Disorders.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goncalves, S., Goldstein, B.J. Pathophysiology of Olfactory Disorders and Potential Treatment Strategies. Curr Otorhinolaryngol Rep 4, 115–121 (2016). https://doi.org/10.1007/s40136-016-0113-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40136-016-0113-5

Keywords

Search

Navigation