title: Neurotrophins and their role in the cochlea.
abstract: Spiral ganglion cell (SGC) degeneration following hair cell loss can be prevented by administration of exogenous neurotrophic factors. Many of these neurotrophic factors, in particular the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been described to be involved in the development of the rodent cochlea. While expression of most of the neurotrophins has decreased to below detectable levels during adulthood (only NT-3 remains highly expressed), their respective receptors remain present in SGCs. Indeed much less is known about the function of neurotrophins in the mature cochlea. Such knowledge is crucial in the search for tools to improve SGC survival following cochlear implantation. In this review, we will critically regard the current experimental findings of neurotrophic treatment of the SGCs in the perspective of fundamental cellular mechanisms underlying neurotrophin signaling. We conclude that, in order to fully apprehend the effects of neurotrophic treatment of degenerating SGCs and in order to consider clinical application of neurotrophins, future research should focus (a) on characterizing the expression pattern of neurotrophins in the cochlea after deafening, (b) on more detailed characterization of functional and morphological changes of SGCs associated with both deafening and neurotrophic treatment and (c) on the possible self-supporting state of SGCs after cessation of short-term neurotrophic treatment.
authors.affiliation: Department of Otorhinolaryngology and Head & Neck Surgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Room G.02.531, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Dyan
authors.initials: D
authors.lastname: Ramekers
authors.forename: Huib
authors.initials: H
authors.lastname: Versnel
authors.forename: Wilko
authors.initials: W
authors.lastname: Grolman
authors.forename: Sjaak F L
authors.initials: SF
authors.lastname: Klis
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D034381:Hearing Loss / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013136:Spiral Ganglion / Q000378:metabolism / Q000473:pathology
chemical_list: D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D017475:Receptors, Nerve Growth Factor