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Distribution of P75 neurotrophin receptor in adult human cochlea—an immunohistochemical study

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Abstract

Mechanisms underlying the unique survival property of human spiral neurons are yet to be explored. P75 (p75NTR) is a low affinity receptor for neurotrophins and is known to interact with Trk receptors to modulate ligand binding and signaling. Up-regulation of this receptor was found to be associated with apoptosis as well as with cell proliferation. Its distribution and injury-induced change in expression pattern in the cochlea have been mainly studied in rodents. There is still no report concerning p75NTR in post-natal human inner ear. We analyzed, for the first time, p75NTR expression in five freshly fixed human cochleae by using immunohistochemistry techniques, including myelin basic protein (MBP) as a myelin sheath marker and TrkB as the human spiral neuron marker, and by using thin optical sectioning of laser confocal microscopy. The inner ear specimens were obtained from adult patients who had normal pure tone thresholds before the surgical procedures, via a trans-cochlear approach for removal of giant posterior cranial fossa meningioma. The expression of p75NTR was investigated and localized in the glial cells, including Schwann cells and satellite glial cells in the Rosenthal canal, in the central nerve bundles within the modiolus, and in the osseous spiral lamina of the human cochleae. The biological significance of p75NTR in human cochlea is discussed.

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Acknowledgement

The authors are grateful for the primary antibody provided as a kind gift by Reichardt, L.F. (Reichardt Laboratory, UCSF Mission Bay, San Francisco, CA, USA).

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Authors and Affiliations

  1. Department of Otolaryngology, Uppsala University Hospital, 75185, Uppsala, Sweden

    Wei Liu, Anders Kinnefors & Helge Rask-Andersen

  2. Department of Otolaryngology and University Clinics Innsbruck (TILAK), University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Rudolf Glueckert

  3. Department of Otolaryngology, University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

    Annelies Schrott-Fischer

  4. Division of Clinical and Functional Anatomy, Department of Anatomy, Histology and Embryology, University of Innsbruck, Muellerstr. 59, A 6020, Innsbruck, Austria

    Mario Bitsche

  5. Department of Surgical Sciences, Section of Otolaryngology, Uppsala University Hospital, 751 85, Uppsala, Sweden

    Wei Liu & Helge Rask-Andersen

Authors
  1. Wei Liu
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  2. Rudolf Glueckert
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  3. Anders Kinnefors
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  4. Annelies Schrott-Fischer
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  5. Mario Bitsche
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  6. Helge Rask-Andersen
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Corresponding authors

Correspondence to Wei Liu or Helge Rask-Andersen.

Additional information

This study was supported by ALF grants from Uppsala University Hospital and Uppsala University and by the Foundation “Tysta Skolan”, the Sellander Foundation, Swedish Deafness Foundation (HRF), and the Austrian Science Foundation (FWF) projectnr. Bo5-15948 and P 22287-B13. Our research is part of the European Community 6th Framework Program on Research, Technological Development and Demonstration (Nanotechnology-based Targeted Drug Delivery; contract number: NMP-2004–3.4.1.5-1-1, project acronym: NANOEAR; NINDC[NIH] 1 R 24 DC 008625).

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Suppl Fig. 1-A

Double immunostaining of TrkB and p75NTR in human cochlea. In the spiral ganglion (a–d), trkB antibody labeled (red) SGN cell bodies, whereas p75NTR antibody stained (green) structures outside the SGNs. Arrowheads in (d) point to several p75NTR-positive cell bodies with much smaller nuclei than those of the SGNs. Blue fluorescence represents DAPI in the nuclei (PDF 200 kb)

Suppl Fig. 1-B

Double immunostaining of TrkB and p75NTR in human cochlea. While trkB antibody labeled (red) the nerve fibers (frame) mainly underneath the outer hair cells, p75NTR antibody labeled (green) the structures in OSL (a-–), with p75NTR terminating at the habenula perforata (long arrows) where Schwann cells end. Some cells in OSL are p75NTR positive in their perikarya (short arrow). Arrowheads indicate the nuclei of the hair cells. Scale bar 50 μm (DOC 1507 kb)

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Liu, W., Glueckert, R., Kinnefors, A. et al. Distribution of P75 neurotrophin receptor in adult human cochlea—an immunohistochemical study. Cell Tissue Res 348, 407–415 (2012). https://doi.org/10.1007/s00441-012-1395-7

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  • DOI: https://doi.org/10.1007/s00441-012-1395-7

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