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

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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.

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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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Authors and Affiliations

  1. Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031, Basel, Switzerland

    Michael Sung, Eric Wei, Soledad Levano, Laura Binkert, Alessia Ramseier, Cristian Setz, Daniel Bodmer & Yves Brand

  2. Departments of Surgery/Otolaryngology, UCSD School of Medicine, 9500 Gilman Drive MC0666, La Jolla, CA, 92093, USA

    Eduardo Chavez, Neha Jain & Allen F. Ryan

  3. Department of Neurosciences, UCSD School of Medicine, 9500 Gilman Drive MC0666, La Jolla, CA, 92093, USA

    Allen F. Ryan

  4. San Diego VA Medical Center, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA

    Allen F. Ryan

  5. Clinic of Otolaryngology, Head and Neck Surgery, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    Michael Sung, Eric Wei, Soledad Levano, Laura Binkert, Alessia Ramseier, Cristian Setz, Daniel Bodmer & Yves Brand

Authors
  1. Michael Sung
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  2. Eric Wei
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  3. Eduardo Chavez
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  8. Cristian Setz
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  9. Daniel Bodmer
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  10. Allen F. Ryan
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  11. Yves Brand
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Corresponding author

Correspondence to Yves Brand.

Additional information

Michael Sung and Eric Wei have contributed equally to this study.

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Sung, M., Wei, E., Chavez, E. et al. Inhibition of MMP-2 but not MMP-9 Influences Inner Ear Spiral Ganglion Neurons In Vitro. Cell Mol Neurobiol 34, 1011–1021 (2014). https://doi.org/10.1007/s10571-014-0077-2

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  • DOI: https://doi.org/10.1007/s10571-014-0077-2

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