Alpha-synuclein deficiency and efferent nerve degeneration in the mouse cochlea: A possible cause of early-onset presbycusis

Objectives/HypothesisEfferent nerves under the outer hair cells (OHCs) play a role in the protection of these cells from loud stimuli. Previously, we showed that cochlear α-synuclein expression is localized to efferent auditory synapses at the base of the OHCs. To prove our hypothesis that α-synuclein deficiency and efferent auditory deficit might be a cause of hearing loss, we compared the morphology of efferent nerve endings and α-synuclein expression within the cochleae of two mouse models of presbycusis.Study designComparative animal study of presbycusis.MethodsThe C57BL/6J(C57) mouse strain, a well-known model of early-onset hearing loss, and the CBA mouse strain, a model of relatively late-onset hearing loss, were examined. Auditory brainstem responses and distortion product otoacoustic emissions were recorded, and cochlear morphology with efferent nerve ending was compared. Western blotting was used to examine α-synuclein expression in the cochlea.ResultsCompared with CBA mice, C57 mice showed earlier onset high-frequency hearing loss and decreased function in OHCs, especially within high-frequency regions. C57 mice demonstrated more severe pathologic changes within the cochlea, particularly within the basal turn, than CBA mice of the same age. Weaker α-synuclein and synaptophysin expression in the efferent nerve endings and cochlear homogenates in C57 mice was observed.ConclusionsOur results support the hypothesis that efferent nerve degeneration, possibly due to differential α-synuclein expression, is a potential cause of early-onset presbycusis. Further studies at the cellular level are necessary to verify our results.

► Hearing and morphology of the cochleae in C57 and CBA mice were compared.
► C57 mice showed early-onset hearing loss and severe degeneration of the cochlea.
► α-synuclein was weakly expressed in the efferent nerves and cochlea of C57 mice.
► CBA mice had good hearing and strong expression of α-synuclein within the cochlea.
► α-synuclein deficiency in the cochlea might be a cause of early-onset hearing loss.