Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons in vitro.
The inner ear spiral ganglion is populated by bipolar neurons connecting the peripheral sensory receptors, the hair cells, with central neurons in auditory brain stem nuclei. Hearing impairment is often a consequence of hair cell death, e.g., from acoustic trauma. When deprived of their peripheral targets, the spiral ganglion neurons (SGNs) progressively degenerate. For effective clinical treatment using cochlear prostheses, it is essential to maintain the SGN population. To investigate their survival dependence, synaptogenesis, and regenerative capacity, adult mouse SGNs were separated from hair cells and studied in vitro in the presence of various neurotrophins and growth factors. Coadministration of fibroblast growth factor 2 (FGF-2) and glial cell line-derived neurotrophic factor (GDNF) provided support for long-term survival, while FGF-2 alone could strongly promote neurite regeneration. Fibroblast growth factor receptor FGFR-3-IIIc was found to upregulate and translocate to the nucleus in surviving SGNs. Surviving SGNs formed contacts with other SGNs after they were deprived of the signals from the hair cells. In coculture experiments, neurites extending from SGNs projected toward hair cells. Interestingly, adult mouse spiral ganglion cells could carry out both symmetric and asymmetric cell division and give rise to new neurons. The authors propose that a combination of FGF-2 and GDNF could be an efficient route for clinical intervention of secondary degeneration of SGNs. The authors also demonstrate that the adult mammalian inner ear retains progenitor cells, which could commit neurogenesis.
Wei
Dongguang
D
Center for Hearing and Communication Research, Karolinska Institutet, Stockholm, Sweden. donwei@ucdavis.edu
Jin
Zhe
Z
Järlebark
Leif
L
Scarfone
Eric
E
Ulfendahl
Mats
M
D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D038081:Organogenesis / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013136:Spiral Ganglion / Q000166:cytology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2