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.