The vulnerability of the auditory sense to noise exposure, demanding environmental conditions, and pharmacological cGMP cascade stimulation in a model for age-related hearing loss in the rat and the gerbil

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URI: http://hdl.handle.net/10900/50720
http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-507204
Dokumentart: Dissertation
Date: 2014-03-24
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biochemie
Advisor: Ruth, Peter (Prof. Dr.)
Day of Oral Examination: 2014-03-24
DDC Classifikation: 570 - Life sciences; biology
Keywords: Noise , Cyclo-GMP , Ratte
Other Keywords:
age-related hearing loss, cGMP, environmental enrichment, noise
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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

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