Neurotrophin survival effects on auditory neurons in vivo [Abstract]

Abstract

Neurotrophic factors, in particular the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are well known to be 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 models of deafness. Indeed, numerous studies have demonstrated that intracochlear application of neurotrophins shortly following deafening can prevent auditory neuron degeneration. Following on from these findings, we have investigated two aspects of the time-course of neurotrophin-induced auditory neuron survival.

Firstly, we tested the longevity of the survival effects of BDNF on auditory neurons in deaf guinea pigs; specifically we aimed to determine if the survival effects of BDNF are maintained beyond the period of treatment, or if sustained delivery is required. Results from this study indicated that while BDNF prevents auditory neuron degeneration during the treatment period, cessation of the trophic support leads to a rapid loss of survival effects. These findings suggest ongoing neurotrophin treatment may be required for maintained auditory neuron survival.

Secondly, we examined the effects of delayed neurotrophin treatment on auditory neuron survival following deafness. Results from this study demonstrated that each of the members of the neurotrophin family BDNF, NT-3, neurotrophin 4/5 (NT-4/5) and nerve growth factor (NGF) - can rescue auditory neurons from degeneration after a two-week period of deafness. These findings show that neurotrophins can be effective survival agents even when the degenerative processes are well underway.

The results of these studies provide further support to the theory that neurotrophic factors may ultimately be able to be used as therapeutic agents for the benefit of the hearing impaired community, but suggest that ongoing treatment, or combined use of alternative therapies, may be necessary.