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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Hauptverfasser: Mirretto Barone, Claudia (VerfasserIn) , Fink, Stefan (VerfasserIn) , Schmidbauer, Dominik (VerfasserIn) , Rousset, Francis (VerfasserIn) , Eickhoff, Holger (VerfasserIn) , Tropitzsch, Anke (VerfasserIn) , Kramer, Benedikt (VerfasserIn) , Senn, Pascal (VerfasserIn) , Glueckert, Rudolf (VerfasserIn) , Rask-Andersen, Helge (VerfasserIn) , Wiesmüller, Karl-Heinz (VerfasserIn) , Löwenheim, Hubert (VerfasserIn) , Müller, Marcus (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21. August 2020
In: Brain Sciences
Year: 2020, Jahrgang: 10, Heft: 9, Pages: 1-19
ISSN:2076-3425
DOI:10.3390/brainsci10090580
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/brainsci10090580
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2076-3425/10/9/580
Volltext
Verfasserangaben: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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Zusammenfassung: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.
Beschreibung:Gesehen am 05.12.2025
Beschreibung:Online Resource
ISSN:2076-3425
DOI:10.3390/brainsci10090580