Investigating age-related hearing loss in the primate cochlea

 

Age-related hearing loss is the most common form of sensorineural hearing loss. Studies from the last years in rodents show that age-related hearing loss is mainly associated with the synaptopathy of ribbon synapses, the loss of inner and outer hair cells (IHC, OHC) and of spiral ganglion neurons (SGN).

To investigate the mechanisms underlying age-related hearing loss in a more human-like model, we studied synaptic and cellular changes in the cochlea of the common Marmoset, an arboreal primate, in the range of 1 to 15 years of age. For our research, we established a multimodal imaging strategy. First, we used a whole mount preparation of the cochlea which we immunostained with antibodies to (1) C-terminal binding protein 2 to label the ribbons of the inner hair cell (IHC) afferent synapse, (2) myosin 6 to identify IHCs and OHCs and (3) parvalbumin to label IHCs and spiral ganglion neurons (SGN). Thus, we were able to quantify hair cell number and synaptic density along the tonotopic axis in animals of different age.

Second, we combined immunohistochemistry, tissue clearing and light sheet microscopy to count neurons of the spiral ganglion. Finally, we used micro focus X-ray tomography with phase contrast reconstruction to quantify SGN number and density. For quantification, also semi-automatic algorithms were established.

In conclusion, while the number of synapses per IHC is highly dependent of its tonotopic region, we find only little variation in synaptic density at a given frequency in animals of different age, suggesting only limited degradation of the inner ear with age in these animals.

Poster-PDF A-1648.pdf

Publication History

Article published online:
13 May 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany