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Cellular and Molecular Neurobiology

, Volume 34, Issue 7, pp 1011–1021 | Cite as

Inhibition of MMP-2 but not MMP-9 Influences Inner Ear Spiral Ganglion Neurons In Vitro

  • Michael Sung
  • Eric Wei
  • Eduardo Chavez
  • Neha Jain
  • Soledad Levano
  • Laura Binkert
  • Alessia Ramseier
  • Cristian Setz
  • Daniel Bodmer
  • Allen F. Ryan
  • Yves Brand
Original Research

Abstract

Matrix metalloproteinases (MMPs) play an important role in modeling of the extracellular matrix. There is increasing evidence that these proteases are important in neurite elongation and axonal guidance during development in the central nervous system and retina. Moreover, they are also expressed after acute injury and can be the key mediators of pathogenesis. However, the role of MMPs in the inner ear is largely unknown. Our group recently demonstrated that general inhibition of MMPs resulted in auditory hair cell loss in vitro. In the present study, we investigated the role of MMPs in inner ear spiral ganglion neuron (SGN) survival, neuritogenesis and neurite extension by blocking MMPs known to be involved in axonal guidance, neurite elongation, and apoptosis in other neuronal systems. Spiral ganglion (SG) explants from 5-day-old Wistar rats were treated with different concentrations of the general MMP inhibitor GM6001, a specific MMP-2 inhibitor, and a specific MMP-9 inhibitor, in vitro. The general inhibitor of MMPs and the specific inhibition of MMP-2 significantly reduced both the number of neurites that extended from SG explants, as well as the length of individual neurites. However, neither the general inhibitor of MMPs nor the specific inhibition of MMP-2 influenced SGN survival. Inhibition of MMP-9 had no influence on SGNs. The data suggest that MMPs, and more specifically MMP-2, influence the growth of developing afferent neurites in the mammalian inner ear in vivo.

Keywords

Extracellular matrix Inner ear Matrix metalloproteinase Spiral ganglion neurons 

Notes

Acknowledgments

This study is supported by Medizinische Abteilung der Margarete und Walter Lichtsteiner-Stiftung, Basel, Switzerland.

Conflict of interest

All authors report no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Michael Sung
    • 1
    • 5
  • Eric Wei
    • 1
    • 5
  • Eduardo Chavez
    • 2
  • Neha Jain
    • 2
  • Soledad Levano
    • 1
    • 5
  • Laura Binkert
    • 1
    • 5
  • Alessia Ramseier
    • 1
    • 5
  • Cristian Setz
    • 1
    • 5
  • Daniel Bodmer
    • 1
    • 5
  • Allen F. Ryan
    • 2
    • 3
    • 4
  • Yves Brand
    • 1
    • 5
  1. 1.Department of BiomedicineUniversity Hospital BaselBaselSwitzerland
  2. 2.Departments of Surgery/OtolaryngologyUCSD School of MedicineLa JollaUSA
  3. 3.Department of NeurosciencesUCSD School of MedicineLa JollaUSA
  4. 4.San Diego VA Medical CenterSan DiegoUSA
  5. 5.Clinic of Otolaryngology, Head and Neck SurgeryUniversity Hospital BaselBaselSwitzerland

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