title: BDNF-induced survival of auditory neurons in vivo: Cessation of treatment leads to accelerated loss of survival effects.
abstract: Neurotrophic factors are important for the development and maintenance of the auditory system. They have also been shown to act as survival factors for auditory neurons in animal deafness models. Studies have demonstrated recently that these neurotrophic factors not only maintain survival of auditory neurons, but that these surviving neurons retain functionality. It remains to be determined, however, if a single administration of a neurotrophic factor is sufficient to maintain auditory neuron survival after loss of hair cells, or if sustained delivery is required. This study investigated the longevity of the survival effects of BDNF on auditory neurons in deafened guinea pigs. Briefly, the left cochleae of deafened guinea pigs were infused with BDNF for 28 days via a mini-osmotic pump, and neuronal survival was analyzed at various stages after the completion of treatment. BDNF treatment prevented the degeneration of auditory neurons that normally is seen after a loss of hair cells, supporting previous studies. Our results indicate, however, that cessation of BDNF treatment leads to an accelerated decline in auditory neuron survival as compared to that observed in deafened, untreated cochleae. These findings indicate that much work remains to be done to establish a technique for the long-term survival of auditory neurons in the deaf ear.
authors.affiliation: Department of Otolaryngology, The University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
authors.forename: Lisa N
authors.initials: LN
authors.lastname: Gillespie
authors.forename: Graeme M
authors.initials: GM
authors.lastname: Clark
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Marzella
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003638:Deafness / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006801:Humans; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D007612:Kanamycin / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007612:Kanamycin