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Eva Degerman

Eva Degerman

Professor

Eva Degerman

Inhibition of phosphodiesterase 3, 4, and 5 induces endolymphatic hydrops in mouse inner ear, as evaluated with repeated 9.4T MRI

Author

  • Eva Degerman
  • Rene in 't Zandt
  • Ann-Kristin Holmén-Pålbrink
  • Lena Eliasson
  • Per Cayé-Thomasen
  • Måns Magnusson

Summary, in English

Conclusion: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. Objective: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling. Method: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry. Results: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule.

Department/s

  • Insulin Signal Transduction
  • Lund University Bioimaging Center
  • Department of Clinical Sciences, Malmö
  • Diabetes - Islet Cell Exocytosis
  • Otorhinolaryngology (Lund)
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017

Language

English

Pages

8-15

Publication/Series

Acta Oto-Laryngologica

Volume

137

Issue

1

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Otorhinolaryngology

Keywords

  • Aquaporin2
  • cilostamide
  • cochlea
  • Ménière’s disease
  • rolipram
  • sildenafil

Status

Published

Research group

  • Insulin Signal Transduction
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 0001-6489