Abstract:
Age-related hearing loss (ARHL) is a complex degenerative disease commonly seen in
elderly people. It is considered as most often sensory impairment in the elderly. ARHL is a
rapidly growing healthcare issue due to the aging of the population. Up to now our knowledge
on the pathology of ARHL was restricted to the loss or dysfunction of outer hair cells that
normally increase the amplitude and frequency selectivity of sound vibrations by
electromechanical feedback. Recently however it was shown that neurodegeneration of
afferent neural fibers in mice can progress over age independent of outer hair cells (OHCs)
loss in mice. In the present study we were able to confirm this finding in the rat and gerbil
animal model. Shown in detail for the rat, an age dependent loss of inner hair cells (IHCs)
ribbons that was used as a correlate of auditory fiber loss was observed together with a
moderate high-frequency hearing loss independent of OHCs dysfunction in the first period of
a rat‟s life. The high frequency hearing loss and IHCs ribbon loss corresponded to a loss of
summed auditory nerve activity shown with auditory brainstem response (ABR) wave I
amplitude loss progressed further with age. Only in the second period of life OHCs
dysfunction could be detected in addition to IHCs synapse deterioration. Interestingly the
progressive decline of auditory nerve fibers over age could not be centrally compensated. In
contrast, we found that young rats could centrally compensate sensory deprivation was
induced by moderate noise exposure. Elderly rats were unable to compensate damage but
remained less sensitive for noise exposure. It appeared that the failure to compensate the
damage and the reduced sensitivity for noise exposure was caused by the loss of auditory
fibers over age and therefore neither fibers nor reduced amplitudes could be reduced further.
In addition over age the brain may have lost the capacity to compensate peripheral damage,
what may go hand in hand with a loss of a capacity for central homeostatic adaptation. We
questioned whether this neurodegenerative effect in the cochlea over age after trauma could
be compensated by environmental enrichment of the housing conditions. In the present study
we could show that environmental enrichment as well as a stimulation of the cGMP cascade
through activation of the soluble guanylate cyclase could counteract the age-related highfrequency
hearing loss. Further studies are essential to analyse to what extend this positive
effects are the result of direct impact on IHCs synapse afferent contacts. The findings are
discussed on the assumptions that a vulnerable part of auditory fibers can be lost over age or
noise. Young animals can compensate an auditory deprivation and only in young animals
environmental enrichment or pharmacological intervention may have beneficial effects. untranslated