[en] Auditory hair cells produce trophic factors that directly affect maturation and survival of auditory neurons. These factors include two members of the neurotrophin family: brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Loss of hair cells, as a result of either noise trauma or ototoxic damage, results in the degeneration of auditory neurons. An in vitro model of early postnatal rat organ of Corti/spiral ganglion explants was used to study the effects of deprivation and supplementation of nerve growth factor (NGF), BDNF, and NT-3 on neuronal survival. Immunolocalization of receptors for these neurotrophins correlated with their effectiveness as promoters of neuronal survival. BDNF affected early neuronal survival, whereas NT-3 was the most important survival factor for maturing auditory neurons. NGF was shown to maintain axonal morphology. Our results support the hypothesis that changes in the expression of these neurotrophins and their specific receptors in the maturing cochlea may control the postnatal processes of neuronal apoptosis and maturation of the innervation of both inner and outer hair cells. The results suggest that these growth factors have potential for preventing neuronal degeneration as well as enhancing the repair of damaged neuronal processes in the traumatized auditory system.
Disciplines :
Otolaryngology
Author, co-author :
Staecker, H.
Galinovic-Schwartz, V.
Liu, W.
Lefèbvre, Philippe ; Université de Liège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie
Bichler E, Spoendlin H, Rauchegge H. Degeneration of cochlear neurons after amikacin intoxication in the rat. Arch Otolaryngol 1983;237:201-7.
Barde Y. Trophic factors and neuronal survival. Neuron 1989;2:1525-34.
Hofer M, Barde Y. Brain derived neurotrophic factor prevents neuronal death in vivo. Nature 1988;331:261-2.
Van De Water TR. Determinants of neuron-sensory receptor cell interaction during development of the inner ear. Hear Res 1986;22:265-77.
Lefebvre PP, Van De Water TR, Represa J, et al. Temporal pattern of nerve growth factor binding in vivo and the in vitro effects of NGF on cultures of developing auditory and vestibular neurons. Acta Otolaryngol (Stockh) 1992;111:304-11.
Lefebvre P, Malgrange B, Staecker H, Moghadassi M, Van De Water TR, Moonen G. Neurotrophins affect the survival and neuritogenesis of adult injured neurons in vitro. Neuroreport 1994;5:865-8.
Ylikoski J, Pirvola U, Moshnyakov M, Palgi J, Arumae U, Saarma M. Expression patterns of neurotrophin and their receptor mRNAs in the rat inner ear. Hear Res 1993;56:69-78.
Bottenstein JE, Sato GH. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci USA 1979;76:514-7.
Ullrich A, Gray A, Berman C, Dull TJ. Human beta nerve growth factor gene sequence is highly homologous to that of mouse. Nature 1983;303:821-4.
Leibrock J, Lottspeich AH, Hofer M, et al. Molecular cloning and expression of brain derived neurotrophic factor. Nature 1989;341:149-52.
Maisonpierre PC, Belluscio L, Squinto S, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science 1990;247:1446-51.
Bailey NT. Statistical methods in biology. London: Hodder and Stoughton, 1985.
Rueda J, De la Sen C, Guiz J, Merchan J. Neuronal loss in the spiral ganglion of young rats. Arch Otolaryngol 1987;104:417-21.
Sobkowicz HM, Rose JE, Scott GL, et al. Neuronal growth in the organ of Corti in culture. In: Giacobini E et al. eds. Tissue culture in neurobiology. New York: Raven Press, 1980.
Staecker H, Cammer M, Rubinstein R, Van De Water TR. A procedure for RT-PCR amplification of mRNAs on histological specimens. Biotechniques 1994;16:76-80.
Smeyne R, Klein R, Schnapp A, et al. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 1994;368:246-9.
Urschel B, Hulsebosch C. Schwann cell-neuronal interactions in the rat involve nerve growth factor. J Comp Neurol 1990; 296:114-22.
Lefebvre P, Van De Water TR, Staecker H, et al. Nerve growth factor stimulates regeneration but not survival of adult auditory neurons in vitro. Acta Otolaryngol (Stockh) 1992;112:288-93.
Avila M, Varela-Nieto I, Romero G, et al. Brain derived neurotrophic factor and neurotrophin 3 support the survival and neuritogenesis response of developing cochleovestibular ganglion neurons. Dev Biol 1993;159:266-75.
Enfors P, Lee K-F, Jaenish R. Mice lacking brain derived neurotrophic factor develop with sensory deficits. Nature 1994;368: 147-50.
Lohof AM, Ip NY, Poo MM. Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 1993;363:350-3.
Farinas I, Jones K, Backus C, Wang X-Y, Reichardt L. Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature 1994;369:658-61.