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 fol lowing aminoglycoside ototoxicity is associated not only with the direct ef fect on the neurons, but also with a loss of neurotrophic factors provided by auditory hair cells. The neurotrophic Factors, including nerve growth fa ctor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT -3), have been reported ia be effective in enhancing neuronal survival agai nst aminoglycoside ototoxicity in vivo. To determine whether 4-methylcatech ol (4-MC), a potent inducer of nerve growth factor synthesis, can protect s piral ganglion neurons after aminoglycoside treatment in vivo, we studied t he 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 tr eated with GM alone. Our results suggest that 4-MC promotes synthesis of NG F (and/or other neurotrophins), which enhances spiral ganglion neuron survi val after gentamicin treatment.