Age-dependency of neurite outgrowth in postnatal mouse cochlear spiral ganglion explants
Background: The spatial gap between cochlear implants (CIs) and the auditory nerve limits frequency selectivity as large populations of spiral ganglion neurons (SGNs) are electrically stimulated synchronously. To improve CI performance, a possible strategy is to promote neurite outgrowth toward the...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
21. August 2020
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| In: |
Brain Sciences
Year: 2020, Volume: 10, Issue: 9, Pages: 1-19 |
| ISSN: | 2076-3425 |
| DOI: | 10.3390/brainsci10090580 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/brainsci10090580 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2076-3425/10/9/580 
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| Author Notes: | Claudia Frick, Stefan Fink, Dominik Schmidbauer, Francis Rousset, Holger Eickhoff, Anke Tropitzsch, Benedikt Kramer, Pascal Senn, Rudolf Glueckert, Helge Rask-Andersen, Karl-Heinz Wiesmüller, Hubert Löwenheim and Marcus Müller |
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| 245 | 1 | 0 | |a Age-dependency of neurite outgrowth in postnatal mouse cochlear spiral ganglion explants |c Claudia Frick, Stefan Fink, Dominik Schmidbauer, Francis Rousset, Holger Eickhoff, Anke Tropitzsch, Benedikt Kramer, Pascal Senn, Rudolf Glueckert, Helge Rask-Andersen, Karl-Heinz Wiesmüller, Hubert Löwenheim and Marcus Müller |
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| 520 | |a Background: The spatial gap between cochlear implants (CIs) and the auditory nerve limits frequency selectivity as large populations of spiral ganglion neurons (SGNs) are electrically stimulated synchronously. To improve CI performance, a possible strategy is to promote neurite outgrowth toward the CI, thereby allowing a discrete stimulation of small SGN subpopulations. Brain-derived neurotrophic factor (BDNF) is effective to stimulate neurite outgrowth from SGNs. Method: TrkB (tropomyosin receptor kinase B) agonists, BDNF, and five known small-molecule BDNF mimetics were tested for their efficacy in stimulating neurite outgrowth in postnatal SGN explants. To modulate Trk receptor-mediated effects, TrkB and TrkC ligands were scavenged by an excess of recombinant receptor proteins. The pan-Trk inhibitor K252a was used to block Trk receptor actions. Results: THF (7,8,3′-trihydroxyflavone) partly reproduced the BDNF effect in postnatal day 7 (P7) mouse cochlear spiral ganglion explants (SGEs), but failed to show effectiveness in P4 SGEs. During the same postnatal period, spontaneous and BDNF-stimulated neurite outgrowth increased. The increased neurite outgrowth in P7 SGEs was not caused by the TrkB/TrkC ligands, BDNF and neurotrophin-3 (NT-3). Conclusions: The age-dependency of induction of neurite outgrowth in SGEs was very likely dependent on presently unidentified factors and/or molecular mechanisms which may also be decisive for the age-dependent efficacy of the small-molecule TrkB receptor agonist THF. | ||
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| 650 | 4 | |a murine postnatal model | |
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| 650 | 4 | |a SGN | |
| 650 | 4 | |a small-molecule BDNF mimetics | |
| 650 | 4 | |a spiral ganglion explant culture | |
| 650 | 4 | |a THF | |
| 650 | 4 | |a Trk receptors | |
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