Neurotrophins support auditory neuron survival in vivo following an extended period of deafness [Abstract]

Abstract

Neurotrophic factors are important for the development and maintenance of the auditory system, and have also been reported to act as survival factors for auditory neurons in animal deafness models. Indeed, studies have demonstrated that application of neurotrophins into the inner ear shortly following deafening can prevent auditory neuron degeneration. However, little is known about the survival effects of delayed neurotrophin treatment, which is a clinically more realistic model. This study examined the capacity of various neurotrophins to support auditory neuron survival after an extended period of deafness in vivo. Specifically, we aimed to determine if the neurotrophins BDNF, NT-3, NT-4/5 and NGF could rescue neurons from degeneration after a two-week period of deafness. Normal hearing guinea pigs were bilaterally deafened; two weeks later the left cochleae were implanted with a mini-osmotic pump, which delivered 200µl of neurotrophin (62.5µg/ml) over a period of 28 days. The right cochleae acted as deafened and untreated internal controls. For all surgical procedures, guinea pigs were anaesthetised using ketamine (40mg/kg) and xylazil (4mg/kg). Delayed treatment with each of the four neurotrophins halted the degeneration of auditory neurons that is normally seen following loss of hair cells, resulting in neuronal survival rates of between 79-87% of normal hearing animals, as compared to only 52% survival in deafened, untreated controls. These results indicate that neurotrophins have the capacity to rescue auditory neurons from degeneration following an extended period of deafness. These findings suggest that neurotrophins may play a role as therapeutic agents in long-term deaf patients.