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Pleiotrophin increases neurite length and number of spiral ganglion neurons in vitro

  • Sebastian Bertram
  • Lars Roll
  • Jacqueline Reinhard
  • Katharina Groß
  • Stefan Dazert
  • Andreas Faissner
  • Stefan VolkensteinEmail author
Research Article

Abstract

Acoustic trauma, aging, genetic defects or ototoxic drugs are causes for sensorineural hearing loss involving sensory hair cell death and secondary degeneration of spiral ganglion neurons. Auditory implants are the only available therapy for severe to profound sensorineural hearing loss when hearing aids do not provide a sufficient speech discrimination anymore. Neurotrophic factors represent potential therapeutic candidates to improve the performance of cochlear implants (CIs) by the support of spiral ganglion neurons (SGNs). Here, we investigated the effect of pleiotrophin (PTN), a well-described neurotrophic factor for different types of neurons that is expressed in the postnatal mouse cochlea. PTN knockout mice exhibit severe deficits in auditory brainstem responses, which indicates the importance of PTN in inner ear development and function and makes it a promising candidate to support SGNs. Using organotypic explants and dissociated SGN cultures, we investigated the influence of PTN on the number of neurons, neurite number and neurite length. PTN significantly increased the number and neurite length of dissociated SGNs. We further verified the expression of important PTN-associated receptors in the SG. mRNA of anaplastic lymphoma kinase, αv integrin, β3 integrin, receptor protein tyrosine phosphatase β/ζ, neuroglycan C, low-density lipoprotein receptor-related protein 1 and syndecan 3 was detected in the inner ear. These results suggest that PTN may be a novel candidate to improve sensorineural hearing loss treatment in the future.

Keywords

Cochlea Hearing loss Neurite growth Neurotrophin Organotypic explant 

Abbreviations

ALK

Anaplastic lymphoma kinase

BDNF

Brain-derived neurotrophic factor

BM

Basic medium

BMP-2

Bone morphogenetic protein-2

CI

Cochlear implant

DRG

Dorsal root ganglion

GDNF

Glial cell line-derived neurotrophic factor

HARP

Heparin affinity regulatory peptide

HB-GAM

Heparin-binding growth-associated molecule

HBBM

Heparin-binding brain mitogen

HBGF-8

Heparin-binding growth factor 8

HC

Hair cell

LIF

Leukemia inhibitory factor

LN

Laminin

LRP1

Low-density lipoprotein receptor-related protein

MK

Midkine

NGC

Neuroglycan C

NGPF1

Neurite growth-promoting factor 1

NT-3

Neurotrophin-3

NT

Neurotrophins

P

Postnatal day

PLL

Poly-l-lysine

PTN

Pleiotrophin

RPTPβ/ζ

Receptor protein tyrosine phosphatase β/ζ

SDC

Syndecan

SG

Spiral ganglion

SGN

Spiral ganglion neuron

SMN

Spinal motor neuron

Notes

Acknowledgements

This study was supported by MED-EL Deutschland GmbH research grant PVBO2012/2. We gratefully acknowledge Susanne Kanabey and Sabine Kindermann for excellent technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

221_2019_5644_MOESM1_ESM.docx (25 kb)
Supplementary material 1 (DOCX 25 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology, Head and Neck Surgery, St. Elisabeth-HospitalRuhr-University BochumBochumGermany
  2. 2.Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and BiotechnologyRuhr-University BochumBochumGermany

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