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


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.

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Anaplastic lymphoma kinase


Brain-derived neurotrophic factor


Basic medium


Bone morphogenetic protein-2


Cochlear implant


Dorsal root ganglion


Glial cell line-derived neurotrophic factor


Heparin affinity regulatory peptide


Heparin-binding growth-associated molecule


Heparin-binding brain mitogen


Heparin-binding growth factor 8


Hair cell


Leukemia inhibitory factor




Low-density lipoprotein receptor-related protein




Neuroglycan C


Neurite growth-promoting factor 1






Postnatal day






Receptor protein tyrosine phosphatase β/ζ




Spiral ganglion


Spiral ganglion neuron


Spinal motor neuron


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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.

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Correspondence to Stefan Volkenstein.

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Bertram, S., Roll, L., Reinhard, J. et al. Pleiotrophin increases neurite length and number of spiral ganglion neurons in vitro. Exp Brain Res 237, 2983–2993 (2019).

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  • Cochlea
  • Hearing loss
  • Neurite growth
  • Neurotrophin
  • Organotypic explant