Protection of auditory neurons from aminoglycoside toxicity by neurotrophin-3.
Hearing is conveyed from the auditory receptors, the hair cells in the organ of Corti, to the brain via the spiral ganglion neurons. Damage or loss of either spiral ganglion neurons or hair cells causes hearing impairment. Such hearing disorders are often permanent and can be caused by therapeutic agents, such as aminoglycoside antibiotics and cisplatin, or by aging, loud sounds, infections and mechanical injury (1). Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of the neurotrohin family of neurotrophic factors that also include nerve growth factor (NGF) and neurotrophin-4/5 (NT-4), are important in development of the neuronal components of the inner ear. We report here that the loss of target innervation and the degeneration of approximately 90% of the adult spiral ganglion neurons caused by aminoglycoside toxicity can be prevented by infusion of the neurotrophic factor, neurotrophin-3 (NT-3) in the membranous labyrinth in guinea pigs. The potency of NT-3 in protecting spiral ganglion neurons from degenerating suggests that neurotrophins may be useful for the treatment of hearing disorders.
Ernfors
P
P
Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institute, Stockholm, Sweden.
Duan
M L
ML
ElShamy
W M
WM
Canlon
B
B
D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D006168:Guinea Pigs; D006311:Hearing Disorders / Q000139:chemically induced / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020933:Neurotrophin 3; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
D000617:Aminoglycosides; D009414:Nerve Growth Factors; D020933:Neurotrophin 3