Age-dependent alterations of medial olivocochlear efferent synapses in the murine cochlea
by Nele Marie Dörje
Date of Examination:2024-11-06
Date of issue:2024-10-11
Advisor:Prof. Dr. Tobias Moser
Referee:Prof. Dr. Tiago Fleming Outeiro
Referee:Prof. Dr. Margarete Schön
Persistent Address:
http://dx.doi.org/10.53846/goediss-10758
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Abstract
English
Age-related hearing loss, also referred to as presbycusis, is defined as bilateral, symmetrical sensorineural hearing loss caused by age-related alterations of the auditory system. Previous studies on ARHL have investigated its characteristics and observed age-related degeneration of peripheral sensory cells and neurons as well as central changes in the auditory pathway. The underlying mechanism(s) of those morphological changes have not been resolved yet. During the last five to ten years many interesting studies have focused on the function and effects of the efferent olivocochlear system and how it might be linked to the etiology and pathogenesis of age-related hearing loss. These studies showed the olivocochlear system, and especially the medial olivocochlear (MOC) system, to have protective effects on cochlear function during the aging process, raising the question of which role the MOC system might be playing in the onset and/or progression of age-related haring loss. In this study, we investigated MOC efferent synapse density in the outer hair cell region of aging CBA/J mice, a model organism for late-onset sensorineural hearing loss. Data from young animals (3 months) was compared to data from animals aged between 10 and 20 months in bimonthly intervals. Apical, middle and basal turns of the cochlea were analyzed separately, representing low, middle and high frequency regions, respectively. Mean efferent MOC innervation density was highest in the middle turn for all age groups. A significant reduction of MOC synapse density on outer hair cells was detected at 20 months of age and affected the middle turn (~15 % reduction) as well as the basal turn (~26 % reduction), while the apical turn remained unaffected. Observed MOC synapse loss occurred independently of the loss of outer hair cells, i.e. the loss of target structures, suggesting reduced efferent innervation density to be an independent factor in cochlear aging. Considering the cochlear frequency regions analyzed, age-dependent MOC synapse loss affected the cochlear basal turn, i.e. the high frequency region, to a greater extent than the middle or low frequency regions, which matches the distribution of sensitivity loss in presbycusis. Morphological efferent MOC synapse loss did not become significant until 20 months of age, which is after the onset of age-related hearing loss in the CBA/J strain, but MOC synapses on OHCs might be non-functional before morphological changes in MOC innervation become evident. Since previous studies showed the MOC system to have protective effects on hearing function during aging, age-dependent efferent MOC synapse loss and reduced MOC effect size might have a negative impact on preexisting presbycusis and serve as a catalysator in the process of age-related hearing loss.
Keywords: presbycusis; age-related hearing loss; olivocochlear efferents; MOC-OHC synapse; cochlear synaptopathy; cochlear efferent synapses
