4-methylcatechol, a potent inducer of nerve growth factor synthesis, protects spiral ganglion neurons from aminoglycoside ototoxicity--preliminary report.
The degeneration of spiral ganglion neurons after hair cell destruction following aminoglycoside ototoxicity is associated not only with the direct effect on the neurons, but also with a loss of neurotrophic factors provided by auditory hair cells. The neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been reported to be effective in enhancing neuronal survival against aminoglycoside ototoxicity in vivo. To determine whether 4-methylcatechol (4-MC), a potent inducer of nerve growth factor synthesis, can protect spiral ganglion neurons after aminoglycoside treatment in vivo, we studied the spiral ganglion neurons of gentamicin (GM)-treated mice with or without 4-MC administration. We found that the number of surviving spiral ganglion neurons of 4-MC-treated animals was significantly greater than for those treated with GM alone. Our results suggest that 4-MC promotes synthesis of NGF (and/or other neurotrophins), which enhances spiral ganglion neuron survival after gentamicin treatment.
Kimura
N
N
Department of Otorhinolaryngology, Okayama University Medical School, Japan. me4606@hp.okayama-u.ac.jp
Nishizaki
K
K
Orita
Y
Y
Masuda
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002396:Catechols / Q000494:pharmacology*; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D002396:Catechols; D005839:Gentamicins; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C018599:4-methylcatechol